3-112202269-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. 13/21 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: 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
• Publications: 35 publications found

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_183061.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9C1	NM_183061.3	MANE Select	c.2303G>T	p.Ser768Ile	missense	Exon 18 of 29	NP_898884.1
	SLC9C1	NM_001320531.2		c.2159G>T	p.Ser720Ile	missense	Exon 17 of 28	NP_001307460.1
	SLC9C1	NR_135297.2		n.1573G>T		non_coding_transcript_exon	Exon 12 of 23

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC9C1	ENST00000305815.10	TSL:2 MANE Select	c.2303G>T	p.Ser768Ile	missense	Exon 18 of 29	ENSP00000306627.5
	SLC9C1	ENST00000487372.5	TSL:1	c.2159G>T	p.Ser720Ile	missense	Exon 17 of 28	ENSP00000420688.1
	SLC9C1	ENST00000471295.1	TSL:5	n.*632G>T		non_coding_transcript_exon	Exon 11 of 22	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

African (AFR) AF: 0.356 AC: 11862 AN: 33342

American (AMR) AF: 0.389 AC: 17230 AN: 44350

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 6737 AN: 26040

East Asian (EAS) AF: 0.348 AC: 13781 AN: 39594

South Asian (SAS) AF: 0.338 AC: 28769 AN: 85100

European-Finnish (FIN) AF: 0.252 AC: 13470 AN: 53360

Middle Eastern (MID) AF: 0.251 AC: 1414 AN: 5632

European-Non Finnish (NFE) AF: 0.271 AC: 300662 AN: 1110098

Other (OTH) 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

African (AFR) AF: 0.351 AC: 14538 AN: 41386

American (AMR) AF: 0.340 AC: 5166 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 938 AN: 3468

East Asian (EAS) AF: 0.360 AC: 1854 AN: 5144

South Asian (SAS) AF: 0.327 AC: 1573 AN: 4810

European-Finnish (FIN) AF: 0.254 AC: 2677 AN: 10538

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18354 AN: 67830

Other (OTH) AF: 0.266 AC: 558 AN: 2098

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 v4.9

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
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.12
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Benign	0.25
Sift	Benign	0.097	T
Sift4G	Uncertain	0.0050	D
Polyphen		0.89	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

Other links and lift over

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