1-173530035-A-T

Variant summary

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

The NM_178527.4(SLC9C2):c.2183T>A(p.Ile728Lys) 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: 31)
• Consequence: SLC9C2 NM_178527.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.542

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.2183T>A	p.Ile728Lys	missense_variant	18/28	ENST00000367714.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9C2	ENST00000367714.4	c.2183T>A	p.Ile728Lys	missense_variant	18/28	1	NM_178527.4	P1
SLC9C2	ENST00000466087.1	n.1517T>A		non_coding_transcript_exon_variant	11/21	1
SLC9C2	ENST00000648789.1	n.788T>A		non_coding_transcript_exon_variant	7/11

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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 26, 2022

The c.2183T>A (p.I728K) alteration is located in exon 18 (coding exon 17) of the SLC9C2 gene. This alteration results from a T to A substitution at nucleotide position 2183, causing the isoleucine (I) at amino acid position 728 to be replaced by a lysine (K). 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	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	11
Dann	Benign	0.79
DEOGEN2	Benign	0.063	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0048	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.10
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.97	D
Vest4		0.56
MutPred		0.62		Loss of catalytic residue at I728 (P = 0.0052);
MVP		0.21
MPC		0.47
ClinPred		0.94	D
GERP RS		-1.9
Varity_R		0.15
gMVP		0.56

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: chr1-173499174;