3-112168965-T-C

Variant names:

• chr3-112168965-T-C
• NM_183061.3:c.3149A>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_183061.3(SLC9C1):​c.3149A>G​(p.Tyr1050Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,098 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC9C1 NM_183061.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.25

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.811

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9C1	NM_183061.3	c.3149A>G	p.Tyr1050Cys	missense_variant	Exon 25 of 29	ENST00000305815.10	NP_898884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9C1	ENST00000305815.10	c.3149A>G	p.Tyr1050Cys	missense_variant	Exon 25 of 29	2	NM_183061.3	ENSP00000306627.5
SLC9C1	ENST00000487372.5	c.3005A>G	p.Tyr1002Cys	missense_variant	Exon 24 of 28	1		ENSP00000420688.1
SLC9C1	ENST00000471295.1	n.*1478A>G		non_coding_transcript_exon_variant	Exon 18 of 22	5		ENSP00000418371.1
SLC9C1	ENST00000471295.1	n.*1478A>G		3_prime_UTR_variant	Exon 18 of 22	5		ENSP00000418371.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460098 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726218

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3149A>G (p.Y1050C) alteration is located in exon 25 (coding exon 24) of the SLC9C1 gene. This alteration results from a A to G substitution at nucleotide position 3149, causing the tyrosine (Y) at amino acid position 1050 to be replaced by a cysteine (C). 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	0.10
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Benign	0.056	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Uncertain	0.10	D
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Uncertain	0.31
Sift	Benign	0.046	D;T
Sift4G	Uncertain	0.010	D;D
Polyphen		1.0	D;D
Vest4		0.73
MutPred		0.39		Loss of catalytic residue at I1049 (P = 0.0558);.;
MVP		0.86
MPC		0.37
ClinPred		0.97	D
GERP RS		6.1
Varity_R		0.20
gMVP		0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-111887812;