15-65624189-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004727.3(SLC24A1):c.109A>T(p.Thr37Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,613,544 control chromosomes in the GnomAD database, including 42,976 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 4217 hom., cov: 31)

Exomes 𝑓: 0.21 ( 38759 hom. )

Consequence

SLC24A1
NM_004727.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0400

Publications

41 publications found

Variant links:

Genes affected

SLC24A1 (HGNC:10975): (solute carrier family 24 member 1) This gene encodes a member of the potassium-dependent sodium/calcium exchanger protein family. The encoded protein plays an important role in sodium/calcium exchange in retinal rod and cone photoreceptors by mediating the extrusion of one calcium ion and one potassium ion in exchange for four sodium ions. Mutations in this gene may play a role in congenital stationary night blindness. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

SLC24A1 Gene-Disease associations (from GenCC):

congenital stationary night blindness 1D
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
congenital stationary night blindness
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SLC24A1 links:

LOC102723464 (HGNC:):

LOC102723464 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.5433449E-6).

BP6

Variant 15-65624189-A-T is Benign according to our data. Variant chr15-65624189-A-T is described in ClinVar as Benign. ClinVar VariationId is 259525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A1	NM_004727.3 link	c.109A>T	p.Thr37Ser	missense_variant	Exon 2 of 10	ENST00000261892.11	NP_004718.1	O60721-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A1	ENST00000261892.11 link	c.109A>T	p.Thr37Ser	missense_variant	Exon 2 of 10	1	NM_004727.3	ENSP00000261892.6		O60721-1

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

30994

AN:

151842

Hom.:

4216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.146

Gnomad EAS

AF:

0.736

Gnomad SAS

AF:

0.342

Gnomad FIN

AF:

0.280

Gnomad MID

AF:

0.155

Gnomad NFE

AF:

0.183

Gnomad OTH

AF:

0.198

GnomAD2 exomes

AF:

0.255

AC:

63538

AN:

249112

AF XY:

0.255

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.267

Gnomad ASJ exome

AF:

0.142

Gnomad EAS exome

AF:

0.737

Gnomad FIN exome

AF:

0.264

Gnomad NFE exome

AF:

0.182

Gnomad OTH exome

AF:

0.213

GnomAD4 exome

AF:

0.208

AC:

304281

AN:

1461584

Hom.:

38759

Cov.:

AF XY:

0.211

AC XY:

153615

AN XY:

727074

show subpopulations

African (AFR)

AF:

0.141

AC:

4736

AN:

33474

American (AMR)

AF:

0.255

AC:

11401

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

3774

AN:

26134

East Asian (EAS)

AF:

0.701

AC:

27841

AN:

39700

South Asian (SAS)

AF:

0.326

AC:

28132

AN:

86246

European-Finnish (FIN)

AF:

0.263

AC:

14027

AN:

53398

Middle Eastern (MID)

AF:

0.170

AC:

981

AN:

5768

European-Non Finnish (NFE)

AF:

0.180

AC:

199903

AN:

1111802

Other (OTH)

AF:

0.223

AC:

13486

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

13567

27134

40701

54268

67835

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7374

14748

22122

29496

36870

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.204

AC:

30999

AN:

151960

Hom.:

4217

Cov.:

AF XY:

0.214

AC XY:

15896

AN XY:

74256

show subpopulations

African (AFR)

AF:

0.142

AC:

5880

AN:

41450

American (AMR)

AF:

0.213

AC:

3257

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.146

AC:

505

AN:

3470

East Asian (EAS)

AF:

0.736

AC:

3787

AN:

5144

South Asian (SAS)

AF:

0.341

AC:

1639

AN:

4812

European-Finnish (FIN)

AF:

0.280

AC:

2955

AN:

10554

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.183

AC:

12408

AN:

67954

Other (OTH)

AF:

0.203

AC:

428

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1167

2334

3500

4667

5834

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

334

668

1002

1336

1670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.195

Hom.:

2805

Bravo

AF:

0.197

TwinsUK

AF:

0.182

AC:

675

ALSPAC

AF:

0.187

AC:

719

ESP6500AA

AF:

0.137

AC:

523

ESP6500EA

AF:

0.170

AC:

1407

ExAC

AF:

0.252

AC:

30452

Asia WGS

AF:

0.464

AC:

1615

AN:

3478

EpiCase

AF:

0.177

EpiControl

AF:

0.173

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Congenital stationary night blindness 1D

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.3

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.021

T;T;.;.;.;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.45

T;T;T;T;.;T

MetaRNN

Benign

0.0000025

T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.7

.;L;L;.;L;L

PhyloP100

0.040

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.7

N;N;N;N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0030

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

1.0

D;P;.;.;.;P

Vest4

0.069

MutPred

0.58

Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);Loss of loop (P = 0.0128);

MPC

0.52

ClinPred

0.022

GERP RS

2.7

PromoterAI

0.0015

Neutral

(source)

Varity_R

0.080

gMVP

0.12

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over