chr3-112169205-A-C

Variant names:

• chr3-112169205-A-C
• rs534678683
• NM_183061.3:c.3043T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_183061.3(SLC9C1):​c.3043T>G​(p.Ser1015Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,190 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC9C1 NM_183061.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425

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 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=0.05228746).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC9C1	NM_183061.3	c.3043T>G	p.Ser1015Ala	missense_variant	Exon 24 of 29	ENST00000305815.10	NP_898884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9C1	ENST00000305815.10	c.3043T>G	p.Ser1015Ala	missense_variant	Exon 24 of 29	2	NM_183061.3	ENSP00000306627.5
SLC9C1	ENST00000487372.5	c.2899T>G	p.Ser967Ala	missense_variant	Exon 23 of 28	1		ENSP00000420688.1
SLC9C1	ENST00000471295.1	n.*1372T>G		non_coding_transcript_exon_variant	Exon 17 of 22	5		ENSP00000418371.1
SLC9C1	ENST00000471295.1	n.*1372T>G		3_prime_UTR_variant	Exon 17 of 22	5		ENSP00000418371.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 249896 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135084

Gnomad AFR exome AF: 0.0000616

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: 6.85e-7 AC: 1 AN: 1460190 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726388

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.78
DEOGEN2	Benign	0.027	T;.
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.040	N
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.052	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.41	N;N
REVEL	Benign	0.048
Sift	Benign	0.58	T;T
Sift4G	Benign	0.57	T;T
Polyphen		0.029	B;B
Vest4		0.24
MutPred		0.34		Gain of glycosylation at Y1016 (P = 0.0403);.;
MVP		0.20
MPC		0.057
ClinPred		0.045	T
GERP RS		0.47
Varity_R		0.041
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs534678683; hg19: chr3-111888052;