chr15-65624106-C-T

Position:

chr15-65624106-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004727.3(SLC24A1):c.26C>T(p.Pro9Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000411 in 1,606,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

SLC24A1
NM_004727.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.81

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036259145).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC24A1	NM_004727.3 link	c.26C>T	p.Pro9Leu	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 link	c.26C>T	p.Pro9Leu	missense_variant	2/10	1	NM_004727.3	ENSP00000261892.6		O60721-1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000206

AC:

AN:

242446

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

131454

show subpopulations

Gnomad AFR exome

AF:

0.000325

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000303

AC:

AN:

1454294

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

723142

show subpopulations

Gnomad4 AFR exome

AF:

0.000453

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000236

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000244

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000145

AC:

AN:

152024

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.000507

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000285

Hom.:

Bravo

AF:

0.0000831

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000414

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 17, 2022

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 9 of the SLC24A1 protein (p.Pro9Leu). This variant is present in population databases (rs375737404, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with SLC24A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 955111). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.56

CADD

Benign

2.4

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0078

T;T;.;.;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0078

LIST_S2

Benign

0.71

T;T;T;T;.;T

M_CAP

Benign

0.022

MetaRNN

Benign

0.036

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.34

.;N;N;.;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.32

N;N;N;N;N;N

REVEL

Benign

0.053

Sift

Benign

0.12

T;T;T;T;T;T

Sift4G

Benign

0.093

T;T;T;T;T;T

Polyphen

0.049

B;B;.;.;.;B

Vest4

0.052

MVP

0.42

MPC

0.22

ClinPred

0.049

GERP RS

-4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.048

gMVP

0.36

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