Variant 3-112169290-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_183061.3(SLC9C1):c.2958T>A(p.Phe986Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00759 in 1,613,200 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0061 ( 11 hom., cov: 33)

Exomes 𝑓: 0.0077 ( 59 hom. )

Consequence

SLC9C1
NM_183061.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.95

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015887707).

BP6

Variant 3-112169290-A-T is Benign according to our data. Variant chr3-112169290-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 774845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9C1	NM_183061.3 linkuse as main transcript	c.2958T>A	p.Phe986Leu	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 linkuse as main transcript	c.2958T>A	p.Phe986Leu	missense_variant	24/29	2	NM_183061.3	ENSP00000306627	P1	Q4G0N8-1
SLC9C1	ENST00000487372.5 linkuse as main transcript	c.2814T>A	p.Phe938Leu	missense_variant	23/28	1		ENSP00000420688		Q4G0N8-2
SLC9C1	ENST00000471295.1 linkuse as main transcript	c.*1287T>A		3_prime_UTR_variant, NMD_transcript_variant	17/22	5		ENSP00000418371

Frequencies

GnomAD3 genomes

AF:

0.00615

AC:

936

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00720

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00668

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00985

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00641

AC:

1605

AN:

250254

Hom.:

AF XY:

0.00631

AC XY:

854

AN XY:

135246

show subpopulations

Gnomad AFR exome

AF:

0.000801

Gnomad AMR exome

AF:

0.00330

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00464

Gnomad FIN exome

AF:

0.00732

Gnomad NFE exome

AF:

0.00991

Gnomad OTH exome

AF:

0.00606

GnomAD4 exome

AF:

0.00774

AC:

11309

AN:

1460828

Hom.:

Cov.:

AF XY:

0.00777

AC XY:

5643

AN XY:

726700

show subpopulations

Gnomad4 AFR exome

AF:

0.000598

Gnomad4 AMR exome

AF:

0.00345

Gnomad4 ASJ exome

AF:

0.00161

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00477

Gnomad4 FIN exome

AF:

0.00758

Gnomad4 NFE exome

AF:

0.00893

Gnomad4 OTH exome

AF:

0.00573

GnomAD4 genome

AF:

0.00615

AC:

937

AN:

152372

Hom.:

Cov.:

AF XY:

0.00632

AC XY:

471

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00719

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00668

Gnomad4 NFE

AF:

0.00985

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00832

Hom.:

Bravo

AF:

0.00528

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00686

AC:

ExAC

AF:

0.00641

AC:

778

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2023	SLC9C1: BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.54

D;.

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.73

MetaRNN

Benign

0.016

T;T

MetaSVM

Uncertain

-0.029

MutationAssessor

Benign

1.5

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.011

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;P

Vest4

0.69

MutPred

0.68

Gain of helix (P = 0.0854);.;

MVP

0.59

MPC

0.39

ClinPred

0.054

GERP RS

3.4

Varity_R

0.38

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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