chr3-112169283-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.64

Variant links:

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]

SLC9C1 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
SLC9C1	NM_183061.3 link	c.2965T>C	p.Cys989Arg	missense_variant	Exon 24 of 29	ENST00000305815.10	NP_898884.1	Q4G0N8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC9C1	ENST00000305815.10 link	c.2965T>C	p.Cys989Arg	missense_variant	Exon 24 of 29	2	NM_183061.3	ENSP00000306627.5	Q4G0N8-1
SLC9C1	ENST00000487372.5 link	c.2821T>C	p.Cys941Arg	missense_variant	Exon 23 of 28	1		ENSP00000420688.1	Q4G0N8-2
SLC9C1	ENST00000471295.1 link	n.*1294T>C		non_coding_transcript_exon_variant	Exon 17 of 22	5		ENSP00000418371.1	F8WCJ0
SLC9C1	ENST00000471295.1 link	n.*1294T>C		3_prime_UTR_variant	Exon 17 of 22	5		ENSP00000418371.1	F8WCJ0

Frequencies

GnomAD3 genomes

AF:

0.00309

AC:

470

AN:

152228

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00295

AC XY:

399

AN XY:

135338

show subpopulations

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.:

Cov.:

AF XY:

0.00382

AC XY:

2774

AN XY:

726826

show subpopulations

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.:

Cov.:

AF XY:

0.00301

AC XY:

224

AN XY:

74506

show subpopulations

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.:

Bravo

AF:

0.00338

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00246

AC:

298

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 16, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLC9C1: BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.37

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

M_CAP

Benign

0.073

MetaRNN

Benign

0.0062

T;T

MetaSVM

Benign

-0.53

MutationAssessor

Benign

1.3

L;.

PrimateAI

Benign

0.37

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over