dbSNP rs1014286: SLC9A4:p.Gly784Ser (chr2-102532641-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001011552.4(SLC9A4):c.2350G>A(p.Gly784Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 1,613,224 control chromosomes in the GnomAD database, including 321,379 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.64 ( 31285 hom., cov: 31)

Exomes 𝑓: 0.63 ( 290094 hom. )

Consequence

SLC9A4
NM_001011552.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.493

Publications

44 publications found

Variant links:

Genes affected

SLC9A4 (HGNC:11077): (solute carrier family 9 member A4) Predicted to enable potassium:proton antiporter activity and sodium:proton antiporter activity. Predicted to be involved in potassium ion transmembrane transport; regulation of intracellular pH; and sodium ion import across plasma membrane. Predicted to act upstream of or within epithelial cell development and gastric acid secretion. Predicted to be located in several cellular components, including apical plasma membrane; basolateral plasma membrane; and vacuolar membrane. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC9A4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.7308365E-6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A4	NM_001011552.4 link	c.2350G>A	p.Gly784Ser	missense_variant	Exon 12 of 12	ENST00000295269.5	NP_001011552.2	Q6AI14
SLC9A4	XM_011511158.2 link	c.2263G>A	p.Gly755Ser	missense_variant	Exon 12 of 12		XP_011509460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9A4	ENST00000295269.5 link	c.2350G>A	p.Gly784Ser	missense_variant	Exon 12 of 12	1	NM_001011552.4	ENSP00000295269.4		Q6AI14

Frequencies

GnomAD3 genomes

AF:

0.640

AC:

97211

AN:

151890

Hom.:

31244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.631

Gnomad AMI

AF:

0.609

Gnomad AMR

AF:

0.675

Gnomad ASJ

AF:

0.601

Gnomad EAS

AF:

0.513

Gnomad SAS

AF:

0.560

Gnomad FIN

AF:

0.721

Gnomad MID

AF:

0.715

Gnomad NFE

AF:

0.642

Gnomad OTH

AF:

0.649

GnomAD2 exomes

AF:

0.634

AC:

158608

AN:

250046

AF XY:

0.629

show subpopulations

Gnomad AFR exome

AF:

0.627

Gnomad AMR exome

AF:

0.735

Gnomad ASJ exome

AF:

0.604

Gnomad EAS exome

AF:

0.500

Gnomad FIN exome

AF:

0.713

Gnomad NFE exome

AF:

0.633

Gnomad OTH exome

AF:

0.639

GnomAD4 exome

AF:

0.629

AC:

918730

AN:

1461218

Hom.:

290094

Cov.:

AF XY:

0.627

AC XY:

455952

AN XY:

726868

show subpopulations

African (AFR)

AF:

0.635

AC:

21245

AN:

33472

American (AMR)

AF:

0.729

AC:

32556

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.599

AC:

15648

AN:

26128

East Asian (EAS)

AF:

0.530

AC:

21036

AN:

39662

South Asian (SAS)

AF:

0.563

AC:

48489

AN:

86194

European-Finnish (FIN)

AF:

0.711

AC:

37958

AN:

53394

Middle Eastern (MID)

AF:

0.686

AC:

3887

AN:

5664

European-Non Finnish (NFE)

AF:

0.630

AC:

700280

AN:

1111680

Other (OTH)

AF:

0.623

AC:

37631

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

19433

38866

58298

77731

97164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18620

37240

55860

74480

93100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.640

AC:

97308

AN:

152006

Hom.:

31285

Cov.:

AF XY:

0.642

AC XY:

47696

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.631

AC:

26146

AN:

41436

American (AMR)

AF:

0.676

AC:

10324

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.601

AC:

2084

AN:

3468

East Asian (EAS)

AF:

0.514

AC:

2653

AN:

5160

South Asian (SAS)

AF:

0.561

AC:

2696

AN:

4808

European-Finnish (FIN)

AF:

0.721

AC:

7629

AN:

10582

Middle Eastern (MID)

AF:

0.721

AC:

212

AN:

294

European-Non Finnish (NFE)

AF:

0.642

AC:

43638

AN:

67966

Other (OTH)

AF:

0.653

AC:

1371

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1788

3576

5364

7152

8940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

794

1588

2382

3176

3970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.633

Hom.:

142443

Bravo

AF:

0.634

TwinsUK

AF:

0.629

AC:

2333

ALSPAC

AF:

0.615

AC:

2370

ESP6500AA

AF:

0.641

AC:

2825

ESP6500EA

AF:

0.635

AC:

5463

ExAC

AF:

0.629

AC:

76373

Asia WGS

AF:

0.560

AC:

1947

AN:

3478

EpiCase

AF:

0.636

EpiControl

AF:

0.641

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.012

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.025

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0079

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0000027

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.49

PhyloP100

-0.49

PrimateAI

Benign

0.21

PROVEAN

Benign

0.49

REVEL

Benign

0.012

Sift

Benign

0.94

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.013

MPC

0.090

ClinPred

0.031

GERP RS

-11

Varity_R

0.020

gMVP

0.092

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over