chr2-102532641-G-A

Variant names:

• chr2-102532641-G-A
• rs1014286
• NM_001011552.4:c.2350G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 44 publications found

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]

ACMG classification

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	c.2350G>A	p.Gly784Ser	missense_variant	Exon 12 of 12	ENST00000295269.5	NP_001011552.2
SLC9A4	XM_011511158.2	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	c.2350G>A	p.Gly784Ser	missense_variant	Exon 12 of 12	1	NM_001011552.4	ENSP00000295269.4

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97211 AN: 151890 Hom.: 31244 Cov.: 31

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

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.: 64 AF XY: 0.627 AC XY: 455952 AN XY: 726868

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

GnomAD4 genome AF: 0.640 AC: 97308 AN: 152006 Hom.: 31285 Cov.: 31 AF XY: 0.642 AC XY: 47696 AN XY: 74294

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

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	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.012
DANN	Benign	0.46
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0079	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.0000027	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.49	N
PhyloP100		-0.49
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.49	N
REVEL	Benign	0.012
Sift	Benign	0.94	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.013
MPC		0.090
ClinPred		0.031	T
GERP RS		-11
Varity_R		0.020
gMVP		0.092
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1014286; hg19: chr2-103149100; COSMIC: COSV54830213;