rs9288938

Positions:

• chr3-112202269-C-A
• chr3-112202269-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183061.3(SLC9C1):​c.2303G>T​(p.Ser768Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,609,404 control chromosomes in the GnomAD database, including 66,578 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.30 (7202 hom., cov: 31)
  • Exomes 𝑓: 0.28 (59376 hom.)
• Consequence: SLC9C1 NM_183061.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

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]

LOC124909407 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048168004).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9C1	NM_183061.3	c.2303G>T	p.Ser768Ile	missense_variant	18/29	ENST00000305815.10	NP_898884.1
LOC124909407	XR_007096003.1	n.6669C>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9C1	ENST00000305815.10	c.2303G>T	p.Ser768Ile	missense_variant	18/29	2	NM_183061.3	ENSP00000306627	P1
SLC9C1	ENST00000487372.5	c.2159G>T	p.Ser720Ile	missense_variant	17/28	1		ENSP00000420688
SLC9C1	ENST00000471295.1	c.*632G>T		3_prime_UTR_variant, NMD_transcript_variant	11/22	5		ENSP00000418371

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45942 AN: 151572 Hom.: 7186 Cov.: 31

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.267

GnomAD3 exomes AF: 0.307 AC: 76640 AN: 249766 Hom.: 12280 AF XY: 0.302 AC XY: 40713 AN XY: 134984

Gnomad AFR exome AF: 0.358

Gnomad AMR exome AF: 0.394

Gnomad ASJ exome AF: 0.263

Gnomad EAS exome AF: 0.388

Gnomad SAS exome AF: 0.341

Gnomad FIN exome AF: 0.252

Gnomad NFE exome AF: 0.267

Gnomad OTH exome AF: 0.279

GnomAD4 exome AF: 0.282 AC: 411480 AN: 1457714 Hom.: 59376 Cov.: 34 AF XY: 0.283 AC XY: 204974 AN XY: 724906

Gnomad4 AFR exome AF: 0.356

Gnomad4 AMR exome AF: 0.389

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.348

Gnomad4 SAS exome AF: 0.338

Gnomad4 FIN exome AF: 0.252

Gnomad4 NFE exome AF: 0.271

Gnomad4 OTH exome AF: 0.292

GnomAD4 genome AF: 0.303 AC: 45993 AN: 151690 Hom.: 7202 Cov.: 31 AF XY: 0.302 AC XY: 22369 AN XY: 74136

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.270

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.266

Alfa AF: 0.277 Hom.: 14784

Bravo AF: 0.311

TwinsUK AF: 0.272 AC: 1008

ALSPAC AF: 0.259 AC: 997

ESP6500AA AF: 0.363 AC: 1601

ESP6500EA AF: 0.271 AC: 2330

ExAC AF: 0.305 AC: 37033

Asia WGS AF: 0.333 AC: 1163 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;.
Eigen	Benign	0.087
Eigen_PC	Benign	0.061
FATHMM_MKL	Benign	0.67	D
MetaRNN	Benign	0.0048	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;.
MutationTaster	Benign	0.99	P;P
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-4.4	D;D
REVEL	Benign	0.25
Sift	Benign	0.097	T;T
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.89	P;P
Vest4		0.25
MPC		0.25
ClinPred		0.052	T
GERP RS		2.0
Varity_R		0.15
gMVP		0.41

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

LitVar

Other links and lift over

dbSNP: rs9288938; hg19: chr3-111921116; COSMIC: COSV59888157;