chr15-65625017-T-G

Position:

chr15-65625017-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004727.3(SLC24A1):c.937T>G(p.Leu313Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0583 in 1,613,076 control chromosomes in the GnomAD database, including 3,062 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L313L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.063 ( 319 hom., cov: 32)

Exomes 𝑓: 0.058 ( 2743 hom. )

Consequence

SLC24A1
NM_004727.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.196

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 links:

SLC24A1 (HGNC:):

SLC24A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019312203).

BP6

Variant 15-65625017-T-G is Benign according to our data. Variant chr15-65625017-T-G is described in ClinVar as [Benign]. Clinvar id is 259527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-65625017-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0885 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A1	NM_004727.3 linkuse as main transcript	c.937T>G	p.Leu313Val	missense_variant	2/10	ENST00000261892.11	NP_004718.1	O60721-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC24A1	ENST00000261892.11 linkuse as main transcript	c.937T>G	p.Leu313Val	missense_variant	2/10	1	NM_004727.3	ENSP00000261892.6		O60721-1

Frequencies

GnomAD3 genomes

AF:

0.0626

AC:

9526

AN:

152094

Hom.:

320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0912

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0412

Gnomad ASJ

AF:

0.0642

Gnomad EAS

AF:

0.0425

Gnomad SAS

AF:

0.0556

Gnomad FIN

AF:

0.0343

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0562

Gnomad OTH

AF:

0.0707

GnomAD3 exomes

AF:

0.0518

AC:

12832

AN:

247760

Hom.:

387

AF XY:

0.0530

AC XY:

7124

AN XY:

134484

show subpopulations

Gnomad AFR exome

AF:

0.0911

Gnomad AMR exome

AF:

0.0278

Gnomad ASJ exome

AF:

0.0704

Gnomad EAS exome

AF:

0.0447

Gnomad SAS exome

AF:

0.0596

Gnomad FIN exome

AF:

0.0323

Gnomad NFE exome

AF:

0.0544

Gnomad OTH exome

AF:

0.0592

GnomAD4 exome

AF:

0.0579

AC:

84585

AN:

1460864

Hom.:

2743

Cov.:

AF XY:

0.0579

AC XY:

42059

AN XY:

726678

show subpopulations

Gnomad4 AFR exome

AF:

0.0940

Gnomad4 AMR exome

AF:

0.0292

Gnomad4 ASJ exome

AF:

0.0669

Gnomad4 EAS exome

AF:

0.0441

Gnomad4 SAS exome

AF:

0.0592

Gnomad4 FIN exome

AF:

0.0313

Gnomad4 NFE exome

AF:

0.0592

Gnomad4 OTH exome

AF:

0.0612

GnomAD4 genome

AF:

0.0625

AC:

9520

AN:

152212

Hom.:

319

Cov.:

AF XY:

0.0612

AC XY:

4553

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0909

Gnomad4 AMR

AF:

0.0411

Gnomad4 ASJ

AF:

0.0642

Gnomad4 EAS

AF:

0.0422

Gnomad4 SAS

AF:

0.0555

Gnomad4 FIN

AF:

0.0343

Gnomad4 NFE

AF:

0.0562

Gnomad4 OTH

AF:

0.0700

Alfa

AF:

0.0584

Hom.:

420

Bravo

AF:

0.0638

TwinsUK

AF:

0.0623

AC:

231

ALSPAC

AF:

0.0620

AC:

239

ESP6500AA

AF:

0.0880

AC:

346

ESP6500EA

AF:

0.0565

AC:

468

ExAC

AF:

0.0519

AC:

6272

Asia WGS

AF:

0.0450

AC:

157

AN:

3478

EpiCase

AF:

0.0604

EpiControl

AF:

0.0600

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 05, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Congenital stationary night blindness 1D

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.3

DANN

Benign

0.31

DEOGEN2

Benign

0.0024

T;T;.;.;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00020

LIST_S2

Benign

0.065

T;T;T;T;.;T

MetaRNN

Benign

0.0019

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N;N;.;N;N

PrimateAI

Benign

0.23

PROVEAN

Benign

0.11

N;N;N;N;N;N

REVEL

Benign

0.033

Sift

Benign

0.15

T;T;T;T;T;T

Sift4G

Benign

0.48

T;T;T;T;T;T

Polyphen

0.0060

B;B;.;.;.;B

Vest4

0.014

MPC

0.22

ClinPred

0.0049

GERP RS

1.3

Varity_R

0.035

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over