Variant 3-112169325-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_183061.3(SLC9C1):c.2923T>C(p.Cys975Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000736 in 1,603,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

SLC9C1
NM_183061.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.95

Variant links:

Genes affected

SLC9C1 (HGNC:31401): (solute carrier family 9 member C1) 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 act upstream of or within flagellated sperm motility. Predicted to be located in motile cilium. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC9C1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.926

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC9C1	NM_183061.3 linkuse as main transcript	c.2923T>C	p.Cys975Arg	missense_variant	24/29	ENST00000305815.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC9C1	ENST00000305815.10 linkuse as main transcript	c.2923T>C	p.Cys975Arg	missense_variant	24/29	2	NM_183061.3	P1	Q4G0N8-1
SLC9C1	ENST00000487372.5 linkuse as main transcript	c.2779T>C	p.Cys927Arg	missense_variant	23/28	1			Q4G0N8-2
SLC9C1	ENST00000471295.1 linkuse as main transcript	c.*1252T>C		3_prime_UTR_variant, NMD_transcript_variant	17/22	5

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000458

AC:

AN:

239996

Hom.:

AF XY:

0.0000539

AC XY:

AN XY:

129974

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000994

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000785

AC:

114

AN:

1451544

Hom.:

Cov.:

AF XY:

0.0000776

AC XY:

AN XY:

721672

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.00

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:

0.0000938

Gnomad4 OTH exome

AF:

0.000150

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

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

Mar 11, 2024

The c.2923T>C (p.C975R) alteration is located in exon 24 (coding exon 23) of the SLC9C1 gene. This alteration results from a T to C substitution at nucleotide position 2923, causing the cysteine (C) at amino acid position 975 to be replaced by an arginine (R). 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

Uncertain

0.46

BayesDel_addAF

Uncertain

0.067

BayesDel_noAF

Uncertain

0.050

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.57

D;.

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Benign

0.65

M_CAP

Uncertain

0.27

MetaRNN

Pathogenic

0.93

D;D

MetaSVM

Pathogenic

0.90

MutationAssessor

Pathogenic

3.0

M;.

MutationTaster

Benign

0.98

D;D

PrimateAI

Benign

0.35

PROVEAN

Pathogenic

-6.1

D;D

REVEL

Uncertain

0.62

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.026

D;D

Polyphen

0.97

D;D

Vest4

0.79

MVP

0.70

MPC

0.42

ClinPred

0.71

GERP RS

5.8

Varity_R

0.93

gMVP

0.63

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.

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