chr3-112202269-C-A

Variant names:

• chr3-112202269-C-A
• rs9288938
• NM_183061.3:c.2303G>T

Variant summary

Our verdict is Benign. The variant received -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. 13/22 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 the same amino acid substitution has been previously reported as Likely benign in 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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC9C1	NM_183061.3	c.2303G>T	p.Ser768Ile	missense_variant	Exon 18 of 29	ENST00000305815.10	NP_898884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC9C1	ENST00000305815.10	c.2303G>T	p.Ser768Ile	missense_variant	Exon 18 of 29	2	NM_183061.3	ENSP00000306627.5
SLC9C1	ENST00000487372.5	c.2159G>T	p.Ser720Ile	missense_variant	Exon 17 of 28	1		ENSP00000420688.1
SLC9C1	ENST00000471295.1	n.*632G>T		non_coding_transcript_exon_variant	Exon 11 of 22	5		ENSP00000418371.1
SLC9C1	ENST00000471295.1	n.*632G>T		3_prime_UTR_variant	Exon 11 of 22	5		ENSP00000418371.1

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

GnomAD2 exomes AF: 0.307 AC: 76640 AN: 249766 AF XY: 0.302

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 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 AC: 11862 AN: 33342

Gnomad4 AMR exome AF: 0.389 AC: 17230 AN: 44350

Gnomad4 ASJ exome AF: 0.259 AC: 6737 AN: 26040

Gnomad4 EAS exome AF: 0.348 AC: 13781 AN: 39594

Gnomad4 SAS exome AF: 0.338 AC: 28769 AN: 85100

Gnomad4 FIN exome AF: 0.252 AC: 13470 AN: 53360

Gnomad4 NFE exome AF: 0.271 AC: 300662 AN: 1110098

Gnomad4 Remaining exome AF: 0.292 AC: 17555 AN: 60198

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 AC: 0.351278 AN: 0.351278

Gnomad4 AMR AF: 0.340 AC: 0.3396 AN: 0.3396

Gnomad4 ASJ AF: 0.270 AC: 0.270473 AN: 0.270473

Gnomad4 EAS AF: 0.360 AC: 0.36042 AN: 0.36042

Gnomad4 SAS AF: 0.327 AC: 0.327027 AN: 0.327027

Gnomad4 FIN AF: 0.254 AC: 0.254033 AN: 0.254033

Gnomad4 NFE AF: 0.271 AC: 0.270588 AN: 0.270588

Gnomad4 OTH AF: 0.266 AC: 0.265968 AN: 0.265968

Alfa AF: 0.281 Hom.: 20602

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;.
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
Mutation Taster		=99/1	polymorphism (auto)

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;