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GeneBe

1-173529924-A-T

Variant summary

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

The NM_178527.4(SLC9C2):c.2294T>A(p.Val765Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,610,854 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000048 ( 1 hom. )

Consequence

SLC9C2
NM_178527.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.312
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]

Genome browser will be placed here

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=0.040371686).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC9C2NM_178527.4 linkuse as main transcriptc.2294T>A p.Val765Asp missense_variant 18/28 ENST00000367714.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC9C2ENST00000367714.4 linkuse as main transcriptc.2294T>A p.Val765Asp missense_variant 18/281 NM_178527.4 P1
SLC9C2ENST00000466087.1 linkuse as main transcriptn.1628T>A non_coding_transcript_exon_variant 11/211
SLC9C2ENST00000648789.1 linkuse as main transcriptn.899T>A non_coding_transcript_exon_variant 7/11

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152148
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000161
AC:
4
AN:
248646
Hom.:
1
AF XY:
0.00000744
AC XY:
1
AN XY:
134340
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000590
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000331
GnomAD4 exome
AF:
0.00000480
AC:
7
AN:
1458706
Hom.:
1
Cov.:
31
AF XY:
0.00000276
AC XY:
2
AN XY:
725536
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000455
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152148
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsDec 03, 2021The c.2294T>A (p.V765D) 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 2294, causing the valine (V) at amino acid position 765 to be replaced by an aspartic acid (D). 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
-0.42
T
BayesDel_noAF
Benign
-0.66
Cadd
Benign
11
Dann
Benign
0.86
DEOGEN2
Benign
0.00057
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.55
T
M_CAP
Benign
0.0048
T
MetaRNN
Benign
0.040
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
-0.34
N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
1.8
N
REVEL
Benign
0.022
Sift
Benign
0.071
T
Sift4G
Benign
0.12
T
Polyphen
0.17
B
Vest4
0.22
MutPred
0.31
Loss of ubiquitination at K761 (P = 0.1055);
MVP
0.092
MPC
0.37
ClinPred
0.026
T
GERP RS
-1.0
Varity_R
0.065
gMVP
0.11

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

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

Other links and lift over

dbSNP: rs771141059; hg19: chr1-173499063; API