1-173524849-G-A

Variant summary

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

The NM_178527.4(SLC9C2):c.2444C>T(p.Ala815Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC9C2 NM_178527.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.91

Genes affected

SLC9C2 (HGNC:28664): (solute carrier family 9 member C2 (putative)) 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 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	UniProt
SLC9C2	NM_178527.4	c.2444C>T	p.Ala815Val	missense_variant	20/28	ENST00000367714.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9C2	ENST00000367714.4	c.2444C>T	p.Ala815Val	missense_variant	20/28	1	NM_178527.4	P1
SLC9C2	ENST00000466087.1	n.1778C>T		non_coding_transcript_exon_variant	13/21	1
SLC9C2	ENST00000648789.1	n.1049C>T		non_coding_transcript_exon_variant	9/11

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jan 07, 2022

The c.2444C>T (p.A815V) alteration is located in exon 20 (coding exon 19) of the SLC9C2 gene. This alteration results from a C to T substitution at nucleotide position 2444, causing the alanine (A) at amino acid position 815 to be replaced by a valine (V). 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	0.29
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
Cadd	Pathogenic	26
Dann	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0098	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
MutationTaster	Benign	0.96	N
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.55
MutPred		0.47		Gain of MoRF binding (P = 0.0853);
MVP		0.57
MPC		0.80
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.21
gMVP		0.39

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: rs1661084598; hg19: chr1-173493988;