Variant 14-92325945-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_153646.4(SLC24A4):c.208G>A(p.Gly70Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,460,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SLC24A4
NM_153646.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.34

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29866505).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC24A4	NM_153646.4 linkuse as main transcript	c.208G>A	p.Gly70Arg	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.208G>A	p.Gly70Arg	missense_variant	2/17	1	NM_153646.4	A1	Q8NFF2-1
SLC24A4	ENST00000393265.6 linkuse as main transcript	c.16G>A	p.Gly6Arg	missense_variant	2/17	1			Q8NFF2-2
SLC24A4	ENST00000676001.1 linkuse as main transcript	c.208G>A	p.Gly70Arg	missense_variant	3/18			A1	Q8NFF2-1
SLC24A4	ENST00000531433.5 linkuse as main transcript	c.208G>A	p.Gly70Arg	missense_variant	3/18	2		P4	Q8NFF2-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1460330

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726418

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Sep 20, 2023

The c.208G>A (p.G70R) alteration is located in exon 2 (coding exon 2) of the SLC24A4 gene. This alteration results from a G to A substitution at nucleotide position 208, causing the glycine (G) at amino acid position 70 to be replaced by an arginine (R). 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

0.068

BayesDel_addAF

Benign

0.010

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

.;.;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.025

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.30

T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.14

.;N;N

MutationTaster

Benign

0.85

D;D;D;D;D

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.15

Sift

Uncertain

0.011

D;T;T

Sift4G

Benign

0.49

T;T;T

Polyphen

0.79, 0.0030

.;P;B

Vest4

0.56

MutPred

0.35

.;Gain of MoRF binding (P = 0.0199);Gain of MoRF binding (P = 0.0199);

MVP

0.81

MPC

0.34

ClinPred

0.72

GERP RS

4.8

Varity_R

0.18

gMVP

0.67

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over