rs1014286

Positions:

• chr2-102532641-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• 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

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.7308365E-6).
• BP6: Variant 2-102532641-G-A is Benign according to our data. Variant chr2-102532641-G-A is described in Lovd as [Benign].
• 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/exons	MANE	Protein	UniProt
SLC9A4	NM_001011552.4	c.2350G>A	p.Gly784Ser	missense_variant	12/12	ENST00000295269.5	NP_001011552.2
SLC9A4	XM_011511158.2	c.2263G>A	p.Gly755Ser	missense_variant	12/12		XP_011509460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A4	ENST00000295269.5	c.2350G>A	p.Gly784Ser	missense_variant	12/12	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

GnomAD3 exomes AF: 0.634 AC: 158608 AN: 250046 Hom.: 50862 AF XY: 0.629 AC XY: 85034 AN XY: 135122

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 SAS exome AF: 0.564

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

Gnomad4 AFR exome AF: 0.635

Gnomad4 AMR exome AF: 0.729

Gnomad4 ASJ exome AF: 0.599

Gnomad4 EAS exome AF: 0.530

Gnomad4 SAS exome AF: 0.563

Gnomad4 FIN exome AF: 0.711

Gnomad4 NFE exome AF: 0.630

Gnomad4 OTH exome AF: 0.623

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

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.561

Gnomad4 FIN AF: 0.721

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.653

Alfa AF: 0.632 Hom.: 74916

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
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

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

Other links and lift over

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