Variant 1-173506858-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178527.4(SLC9C2):c.3223C>G(p.Gln1075Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000121 in 1,611,108 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

SLC9C2
NM_178527.4 missense, splice_region

Scores

Splicing: ADA: 0.1094

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.16

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.041968346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9C2	NM_178527.4 linkuse as main transcript	c.3223C>G	p.Gln1075Glu	missense_variant, splice_region_variant	25/28	ENST00000367714.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9C2	ENST00000367714.4 linkuse as main transcript	c.3223C>G	p.Gln1075Glu	missense_variant, splice_region_variant	25/28	1	NM_178527.4	P1
SLC9C2	ENST00000466087.1 linkuse as main transcript	n.2557C>G		splice_region_variant, non_coding_transcript_exon_variant	18/21	1

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000245

AC:

AN:

248570

Hom.:

AF XY:

0.000216

AC XY:

AN XY:

134318

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00430

Gnomad EAS exome

AF:

0.000383

Gnomad SAS exome

AF:

0.0000333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000533

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.000120

AC:

175

AN:

1458844

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

725700

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00438

Gnomad4 EAS exome

AF:

0.000253

Gnomad4 SAS exome

AF:

0.0000466

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000131

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000273

Hom.:

Bravo

AF:

0.000204

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000206

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.3223C>G (p.Q1075E) alteration is located in exon 25 (coding exon 24) of the SLC9C2 gene. This alteration results from a C to G substitution at nucleotide position 3223, causing the glutamine (Q) at amino acid position 1075 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

0.089

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.37

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.041

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.62

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.68

M_CAP

Benign

0.0098

MetaRNN

Benign

0.042

MetaSVM

Benign

-1.2

MutationAssessor

Pathogenic

2.9

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.2

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.56

MVP

0.62

MPC

0.89

ClinPred

0.23

GERP RS

4.8

Varity_R

0.53

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.11

dbscSNV1_RF

Benign

0.34

SpliceAI score (max)

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over