chr3-112179560-A-G

Variant names:

• chr3-112179560-A-G
• rs373849945
• NM_183061.3:c.2890T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_183061.3(SLC9C1):​c.2890T>C​(p.Tyr964His) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,454,016 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC9C1 NM_183061.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.72

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9C1	NM_183061.3	c.2890T>C	p.Tyr964His	missense_variant	Exon 23 of 29	ENST00000305815.10	NP_898884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9C1	ENST00000305815.10	c.2890T>C	p.Tyr964His	missense_variant	Exon 23 of 29	2	NM_183061.3	ENSP00000306627.5
SLC9C1	ENST00000487372.5	c.2746T>C	p.Tyr916His	missense_variant	Exon 22 of 28	1		ENSP00000420688.1
SLC9C1	ENST00000471295.1	n.*1219T>C		non_coding_transcript_exon_variant	Exon 16 of 22	5		ENSP00000418371.1
SLC9C1	ENST00000471295.1	n.*1219T>C		3_prime_UTR_variant	Exon 16 of 22	5		ENSP00000418371.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000409 AC: 1 AN: 244306 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 131934

Gnomad AFR exome AF: 0.0000626

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1454016 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 722764

Gnomad4 AFR exome AF: 0.0000301

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Uncertain	0.71	D
MutationAssessor	Pathogenic	3.1	M;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.0	D;D
REVEL	Uncertain	0.57
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	D;D
Vest4		0.50
MutPred		0.74		Loss of sheet (P = 0.0181);.;
MVP		0.85
MPC		0.40
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.56
gMVP		0.51

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

Other links and lift over

dbSNP: rs373849945; hg19: chr3-111898407;