3-112169283-A-G

Position:

• chr3-112169283-A-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_183061.3(SLC9C1):​c.2965T>C​(p.Cys989Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00385 in 1,613,390 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (18 hom.)
• Consequence: SLC9C1 NM_183061.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.64

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 Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006165296).
• BP6: Variant 3-112169283-A-G is Benign according to our data. Variant chr3-112169283-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 771856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAdExome4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9C1	NM_183061.3	c.2965T>C	p.Cys989Arg	missense_variant	24/29	ENST00000305815.10	NP_898884.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9C1	ENST00000305815.10	c.2965T>C	p.Cys989Arg	missense_variant	24/29	2	NM_183061.3	ENSP00000306627	P1
SLC9C1	ENST00000487372.5	c.2821T>C	p.Cys941Arg	missense_variant	23/28	1		ENSP00000420688
SLC9C1	ENST00000471295.1	c.*1294T>C		3_prime_UTR_variant, NMD_transcript_variant	17/22	5		ENSP00000418371

Frequencies

GnomAD3 genomes AF: 0.00309 AC: 470 AN: 152228 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000940

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00445

Gnomad OTH AF: 0.00622

GnomAD3 exomes AF: 0.00282 AC: 705 AN: 250380 Hom.: 3 AF XY: 0.00295 AC XY: 399 AN XY: 135338

Gnomad AFR exome AF: 0.000616

Gnomad AMR exome AF: 0.00542

Gnomad ASJ exome AF: 0.00318

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000197

Gnomad FIN exome AF: 0.0000926

Gnomad NFE exome AF: 0.00392

Gnomad OTH exome AF: 0.00410

GnomAD4 exome AF: 0.00393 AC: 5743 AN: 1461044 Hom.: 18 Cov.: 31 AF XY: 0.00382 AC XY: 2774 AN XY: 726826

Gnomad4 AFR exome AF: 0.000389

Gnomad4 AMR exome AF: 0.00567

Gnomad4 ASJ exome AF: 0.00318

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000244

Gnomad4 FIN exome AF: 0.000244

Gnomad4 NFE exome AF: 0.00460

Gnomad4 OTH exome AF: 0.00381

GnomAD4 genome AF: 0.00308 AC: 469 AN: 152346 Hom.: 1 Cov.: 32 AF XY: 0.00301 AC XY: 224 AN XY: 74506

Gnomad4 AFR AF: 0.000938

Gnomad4 AMR AF: 0.00660

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00445

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00391 Hom.: 3

Bravo AF: 0.00338

TwinsUK AF: 0.00270 AC: 10

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00477 AC: 41

ExAC AF: 0.00246 AC: 298

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 16, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	SLC9C1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	6.7
DANN	Benign	0.55
DEOGEN2	Uncertain	0.47	T;.
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.038	N
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.0062	T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.3	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.20
Sift	Benign	0.49	T;T
Sift4G	Benign	0.26	T;T
Polyphen		0.0060	B;B
Vest4		0.28
MVP		0.26
MPC		0.097
ClinPred		0.0030	T
GERP RS		1.7
Varity_R		0.14
gMVP		0.48

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: rs140783319; hg19: chr3-111888130; COSMIC: COSV99997653;