2-102532641-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001011552.4(SLC9A4):​c.2350G>C​(p.Gly784Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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: not found (cov: 31)
• Consequence: SLC9A4 NM_001011552.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.493
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06726432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9A4	NM_001011552.4	c.2350G>C	p.Gly784Arg	missense_variant	Exon 12 of 12	ENST00000295269.5	NP_001011552.2
SLC9A4	XM_011511158.2	c.2263G>C	p.Gly755Arg	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>C	p.Gly784Arg	missense_variant	Exon 12 of 12	1	NM_001011552.4	ENSP00000295269.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 64

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.016
DANN	Benign	0.30
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.49
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.012
Sift	Uncertain	0.021	D
Sift4G	Uncertain	0.052	T
Polyphen		0.0	B
Vest4		0.044
MutPred		0.24		Gain of MoRF binding (P = 0.0312);
MVP		0.092
MPC		0.11
ClinPred		0.11	T
GERP RS		-11
Varity_R		0.043
gMVP		0.086
Mutation Taster		=100/0	polymorphism

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;