rs34363823

Variant names:

• chr15-65625011-G-C
• rs34363823
• NM_004727.3:c.931G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004727.3(SLC24A1):​c.931G>C​(p.Val311Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00796 in 1,612,910 control chromosomes in the GnomAD database, including 145 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 0.012 (30 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (115 hom.)
• Consequence: SLC24A1 NM_004727.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.934
• Publications: 12 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0034194887).
• BP6: Variant 15-65625011-G-C is Benign according to our data. Variant chr15-65625011-G-C is described in ClinVar as Benign. ClinVar VariationId is 195228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0122 (1851/152290) while in subpopulation SAS AF = 0.0402 (194/4828). AF 95% confidence interval is 0.0356. There are 30 homozygotes in GnomAd4. There are 905 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC24A1	NM_004727.3	c.931G>C	p.Val311Leu	missense_variant	Exon 2 of 10	ENST00000261892.11	NP_004718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC24A1	ENST00000261892.11	c.931G>C	p.Val311Leu	missense_variant	Exon 2 of 10	1	NM_004727.3	ENSP00000261892.6

Frequencies

GnomAD3 genomes AF: 0.0121 AC: 1847 AN: 152172 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.0283

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00615

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0399

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00469

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00963 AC: 2385 AN: 247668 AF XY: 0.0110

Gnomad AFR exome AF: 0.0300

Gnomad AMR exome AF: 0.00360

Gnomad ASJ exome AF: 0.00659

Gnomad EAS exome AF: 0.000724

Gnomad FIN exome AF: 0.00168

Gnomad NFE exome AF: 0.00478

Gnomad OTH exome AF: 0.00599

GnomAD4 exome AF: 0.00752 AC: 10987 AN: 1460620 Hom.: 115 Cov.: 35 AF XY: 0.00834 AC XY: 6062 AN XY: 726558

African (AFR) AF: 0.0293 AC: 978 AN: 33412

American (AMR) AF: 0.00399 AC: 178 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00588 AC: 153 AN: 26010

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39690

South Asian (SAS) AF: 0.0360 AC: 3106 AN: 86208

European-Finnish (FIN) AF: 0.00128 AC: 68 AN: 53274

Middle Eastern (MID) AF: 0.00833 AC: 48 AN: 5764

European-Non Finnish (NFE) AF: 0.00531 AC: 5903 AN: 1111326

Other (OTH) AF: 0.00902 AC: 544 AN: 60322

GnomAD4 genome AF: 0.0122 AC: 1851 AN: 152290 Hom.: 30 Cov.: 32 AF XY: 0.0122 AC XY: 905 AN XY: 74458

African (AFR) AF: 0.0283 AC: 1174 AN: 41554

American (AMR) AF: 0.00614 AC: 94 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00806 AC: 28 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5186

South Asian (SAS) AF: 0.0402 AC: 194 AN: 4828

European-Finnish (FIN) AF: 0.000941 AC: 10 AN: 10628

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00469 AC: 319 AN: 68004

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.00642 Hom.: 4

Bravo AF: 0.0125

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00649 AC: 25

ESP6500AA AF: 0.0295 AC: 116

ESP6500EA AF: 0.00628 AC: 52

ExAC AF: 0.0104 AC: 1256

Asia WGS AF: 0.0250 AC: 88 AN: 3478

EpiCase AF: 0.00671

EpiControl AF: 0.00617

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Mar 11, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital stationary night blindness 1D Benign:1

Mar 06, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.2
DANN	Benign	0.86
DEOGEN2	Benign	0.020	T;T;.;.;.;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.83	T;T;T;T;.;T
MetaRNN	Benign	0.0034	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.6	.;L;L;.;L;L
PhyloP100		0.93
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.95	N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Uncertain	0.013	D;D;D;D;D;D
Sift4G	Uncertain	0.035	D;D;D;D;D;D
Polyphen		0.89	P;B;.;.;.;B
Vest4		0.063
MPC		0.21
ClinPred		0.0013	T
GERP RS		0.28
Varity_R		0.092
gMVP		0.18
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs34363823; hg19: chr15-65917349;