Variant 14-92325911-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_153646.4(SLC24A4):c.174G>A(p.Thr58=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 1,612,866 control chromosomes in the GnomAD database, including 790,738 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.94 ( 68466 hom., cov: 32)

Exomes 𝑓: 0.99 ( 722272 hom. )

Consequence

SLC24A4
NM_153646.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.64

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 14-92325911-G-A is Benign according to our data. Variant chr14-92325911-G-A is described in ClinVar as [Benign]. Clinvar id is 1277530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.64 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A4	NM_153646.4 linkuse as main transcript	c.174G>A	p.Thr58=	synonymous_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.174G>A	p.Thr58=	synonymous_variant	2/17	1	NM_153646.4	A1	Q8NFF2-1
SLC24A4	ENST00000393265.6 linkuse as main transcript	c.-19G>A		5_prime_UTR_variant	2/17	1			Q8NFF2-2
SLC24A4	ENST00000676001.1 linkuse as main transcript	c.174G>A	p.Thr58=	synonymous_variant	3/18			A1	Q8NFF2-1
SLC24A4	ENST00000531433.5 linkuse as main transcript	c.174G>A	p.Thr58=	synonymous_variant	3/18	2		P4	Q8NFF2-3

Frequencies

GnomAD3 genomes

AF:

0.944

AC:

143723

AN:

152210

Hom.:

68420

Cov.:

show subpopulations

Gnomad AFR

AF:

0.807

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.978

Gnomad ASJ

AF:

0.998

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

0.987

Gnomad NFE

AF:

0.999

Gnomad OTH

AF:

0.959

GnomAD3 exomes

AF:

0.985

AC:

245837

AN:

249466

Hom.:

121396

AF XY:

0.989

AC XY:

133348

AN XY:

134778

show subpopulations

Gnomad AFR exome

AF:

0.804

Gnomad AMR exome

AF:

0.990

Gnomad ASJ exome

AF:

0.998

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

0.999

Gnomad OTH exome

AF:

0.990

GnomAD4 exome

AF:

0.994

AC:

1451835

AN:

1460538

Hom.:

722272

Cov.:

AF XY:

0.995

AC XY:

722643

AN XY:

726404

show subpopulations

Gnomad4 AFR exome

AF:

0.799

Gnomad4 AMR exome

AF:

0.988

Gnomad4 ASJ exome

AF:

0.999

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.986

GnomAD4 genome

AF:

0.944

AC:

143826

AN:

152328

Hom.:

68466

Cov.:

AF XY:

0.946

AC XY:

70496

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.807

Gnomad4 AMR

AF:

0.978

Gnomad4 ASJ

AF:

0.998

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.959

Alfa

AF:

0.973

Hom.:

43833

Bravo

AF:

0.936

Asia WGS

AF:

0.986

AC:

3429

AN:

3478

EpiCase

AF:

0.999

EpiControl

AF:

0.999

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	GeneDx	Jun 09, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.61

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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