1-173521364-A-C

Position:

• chr1-173521364-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_178527.4(SLC9C2):​c.2676T>G​(p.Asp892Glu) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 29)
• Consequence: SLC9C2 NM_178527.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.458

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]

SLC9C2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28256086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9C2	NM_178527.4	c.2676T>G	p.Asp892Glu	missense_variant	22/28	ENST00000367714.4	NP_848622.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9C2	ENST00000367714.4	c.2676T>G	p.Asp892Glu	missense_variant	22/28	1	NM_178527.4	ENSP00000356687.3
SLC9C2	ENST00000466087.1	n.2010T>G		non_coding_transcript_exon_variant	15/21	1
SLC9C2	ENST00000648789.1	n.1281T>G		non_coding_transcript_exon_variant	11/11

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 29

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

Jun 02, 2024

The c.2676T>G (p.D892E) alteration is located in exon 22 (coding exon 21) of the SLC9C2 gene. This alteration results from a T to G substitution at nucleotide position 2676, causing the aspartic acid (D) at amino acid position 892 to be replaced by a glutamic acid (E). 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	0.20
BayesDel_addAF	Uncertain	0.025	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.074	D
MetaRNN	Benign	0.28	T
MetaSVM	Uncertain	-0.23	T
MutationAssessor	Benign	1.5	L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.41
Sift	Benign	0.039	D
Sift4G	Benign	0.20	T
Polyphen		0.89	P
Vest4		0.20
MutPred		0.52		Gain of sheet (P = 0.0344);
MVP		0.52
MPC		0.50
ClinPred		0.57	D
GERP RS		-0.37
Varity_R		0.061
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr1-173490503;