Variant 14-92323850-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_153646.4(SLC24A4):c.20T>C(p.Leu7Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,588,906 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

SLC24A4
NM_153646.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0690

Variant links:

Genes affected

SLC24A4 (HGNC:10978): (solute carrier family 24 member 4) This gene encodes a sodium/potassium/calcium exchange protein. The encoded antiporter transports one calcium and one potassium ion in exchange for four sodium ions and has been implicated in amelogenesis and enamel maturation. Certain variants in this gene have been associated with skin, hair, and eye pigmentation, while other variants have been identified in people with hypomaturation-type amelogenesis imperfecta. [provided by RefSeq, Nov 2023]

SLC24A4 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=0.02008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A4	NM_153646.4 linkuse as main transcript	c.20T>C	p.Leu7Pro	missense_variant	1/17	ENST00000532405.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A4	ENST00000532405.6 linkuse as main transcript	c.20T>C	p.Leu7Pro	missense_variant	1/17	1	NM_153646.4	A1	Q8NFF2-1
SLC24A4	ENST00000393265.6 linkuse as main transcript	c.-63+1215T>C		intron_variant		1			Q8NFF2-2
SLC24A4	ENST00000676001.1 linkuse as main transcript	c.20T>C	p.Leu7Pro	missense_variant	2/18			A1	Q8NFF2-1
SLC24A4	ENST00000531433.5 linkuse as main transcript	c.20T>C	p.Leu7Pro	missense_variant	2/18	2		P4	Q8NFF2-3

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000159

AC:

AN:

213910

Hom.:

AF XY:

0.000180

AC XY:

AN XY:

116540

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000716

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000121

AC:

174

AN:

1436696

Hom.:

Cov.:

AF XY:

0.000140

AC XY:

100

AN XY:

713786

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00151

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000155

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000976

Gnomad4 OTH exome

AF:

0.000134

GnomAD4 genome

AF:

0.000105

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000304

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000993

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 17, 2023

The c.20T>C (p.L7P) alteration is located in exon 1 (coding exon 1) of the SLC24A4 gene. This alteration results from a T to C substitution at nucleotide position 20, causing the leucine (L) at amino acid position 7 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.14

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.41

T;T

M_CAP

Uncertain

0.088

MetaRNN

Benign

0.020

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

0.83

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.21

N;N

REVEL

Benign

0.054

Sift

Benign

0.053

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.0

B;.

Vest4

0.16

MutPred

0.39

Gain of disorder (P = 0.0175);Gain of disorder (P = 0.0175);

MVP

0.49

MPC

0.45

ClinPred

0.039

GERP RS

-2.2

Varity_R

0.050

gMVP

0.72

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