2-102479128-G-C

Position:

• chr2-102479128-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000295269.5(SLC9A4):​c.546G>C​(p.Gln182His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC9A4 ENST00000295269.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A4	NM_001011552.4	c.546G>C	p.Gln182His	missense_variant	2/12	ENST00000295269.5	NP_001011552.2
SLC9A4	XM_011511158.2	c.546G>C	p.Gln182His	missense_variant	2/12		XP_011509460.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A4	ENST00000295269.5	c.546G>C	p.Gln182His	missense_variant	2/12	1	NM_001011552.4	ENSP00000295269	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 25, 2023

The c.546G>C (p.Q182H) alteration is located in exon 2 (coding exon 2) of the SLC9A4 gene. This alteration results from a G to C substitution at nucleotide position 546, causing the glutamine (Q) at amino acid position 182 to be replaced by a histidine (H). 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	0.14
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.6	M
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.7	D
REVEL	Benign	0.20
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.042	D
Polyphen		0.12	B
Vest4		0.80
MutPred		0.43		Loss of catalytic residue at Q182 (P = 0.0965);
MVP		0.60
MPC		0.11
ClinPred		0.96	D
GERP RS		1.1
Varity_R		0.53
gMVP		0.52

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-103095587;