Variant chr3-112169045-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_183061.3(SLC9C1):c.3069G>T(p.Met1023Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,440,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC9C1
NM_183061.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25156683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9C1	NM_183061.3 link	c.3069G>T	p.Met1023Ile	missense_variant	25/29	ENST00000305815.10	NP_898884.1	Q4G0N8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC9C1	ENST00000305815.10 link	c.3069G>T	p.Met1023Ile	missense_variant	25/29	2	NM_183061.3	ENSP00000306627.5	Q4G0N8-1
SLC9C1	ENST00000487372.5 link	c.2925G>T	p.Met975Ile	missense_variant	24/28	1		ENSP00000420688.1	Q4G0N8-2
SLC9C1	ENST00000471295.1 link	n.*1398G>T		non_coding_transcript_exon_variant	18/22	5		ENSP00000418371.1	F8WCJ0
SLC9C1	ENST00000471295.1 link	n.*1398G>T		3_prime_UTR_variant	18/22	5		ENSP00000418371.1	F8WCJ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1440812

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715754

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 28, 2024

The c.3069G>T (p.M1023I) alteration is located in exon 25 (coding exon 24) of the SLC9C1 gene. This alteration results from a G to T substitution at nucleotide position 3069, causing the methionine (M) at amino acid position 1023 to be replaced by an isoleucine (I). 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

0.32

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.069

T;.

Eigen

Benign

0.023

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.85

M_CAP

Benign

0.036

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.58

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.20

Sift

Benign

0.059

T;T

Sift4G

Uncertain

0.023

D;D

Polyphen

0.52

P;B

Vest4

0.37

MutPred

0.33

Gain of sheet (P = 0.0477);.;

MVP

0.52

MPC

0.14

ClinPred

0.65

GERP RS

5.2

Varity_R

0.27

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over