Variant 14-92325969-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_153646.4(SLC24A4):c.232A>G(p.Thr78Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000826 in 1,605,836 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00065 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00084 ( 5 hom. )

Consequence

SLC24A4
NM_153646.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.55

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008490115).

BP6

Variant 14-92325969-A-G is Benign according to our data. Variant chr14-92325969-A-G is described in ClinVar as [Benign]. Clinvar id is 723341.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A4	NM_153646.4 linkuse as main transcript	c.232A>G	p.Thr78Ala	missense_variant	2/17	ENST00000532405.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC24A4	ENST00000532405.6 linkuse as main transcript	c.232A>G	p.Thr78Ala	missense_variant	2/17	1	NM_153646.4	A1	Q8NFF2-1
SLC24A4	ENST00000393265.6 linkuse as main transcript	c.40A>G	p.Thr14Ala	missense_variant	2/17	1			Q8NFF2-2
SLC24A4	ENST00000676001.1 linkuse as main transcript	c.232A>G	p.Thr78Ala	missense_variant	3/18			A1	Q8NFF2-1
SLC24A4	ENST00000531433.5 linkuse as main transcript	c.232A>G	p.Thr78Ala	missense_variant	3/18	2		P4	Q8NFF2-3

Frequencies

GnomAD3 genomes

AF:

0.000657

AC:

100

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00981

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00117

AC:

291

AN:

248288

Hom.:

AF XY:

0.00118

AC XY:

158

AN XY:

134186

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00128

Gnomad ASJ exome

AF:

0.00978

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.0000469

Gnomad NFE exome

AF:

0.000791

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.000844

AC:

1227

AN:

1453498

Hom.:

Cov.:

AF XY:

0.000842

AC XY:

609

AN XY:

723352

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.0107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00158

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000584

Gnomad4 OTH exome

AF:

0.00143

GnomAD4 genome

AF:

0.000650

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00981

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.000740

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00121

AC:

147

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

.;.;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.0085

T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

2.0

.;M;M

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.22

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.011

D;D;D

Polyphen

0.86, 0.44

.;P;B

Vest4

0.53

MVP

0.84

MPC

0.41

ClinPred

0.054

GERP RS

5.7

Varity_R

0.27

gMVP

0.33

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