Variant chr3-112167223-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_183061.3(SLC9C1):c.3362T>C(p.Ile1121Thr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000448 in 1,606,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

SLC9C1
NM_183061.3 missense, splice_region

Scores

Splicing: ADA: 0.00002121

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.61

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0333651).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9C1	NM_183061.3 linkuse as main transcript	c.3362T>C	p.Ile1121Thr	missense_variant, splice_region_variant	26/29	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.3362T>C	p.Ile1121Thr	missense_variant, splice_region_variant	26/29	2	NM_183061.3	ENSP00000306627	P1	Q4G0N8-1
SLC9C1	ENST00000487372.5 linkuse as main transcript	c.3218T>C	p.Ile1073Thr	missense_variant, splice_region_variant	25/28	1		ENSP00000420688		Q4G0N8-2
SLC9C1	ENST00000471295.1 linkuse as main transcript	c.*1691T>C		splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant	19/22	5		ENSP00000418371

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000974

AC:

AN:

246422

Hom.:

AF XY:

0.0000525

AC XY:

AN XY:

133314

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000424

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000136

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.000333

GnomAD4 exome

AF:

0.0000440

AC:

AN:

1454774

Hom.:

Cov.:

AF XY:

0.0000456

AC XY:

AN XY:

723584

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000393

Gnomad4 ASJ exome

AF:

0.000193

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000188

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.0000999

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000594

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 08, 2024

The c.3362T>C (p.I1121T) alteration is located in exon 26 (coding exon 25) of the SLC9C1 gene. This alteration results from a T to C substitution at nucleotide position 3362, causing the isoleucine (I) at amino acid position 1121 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0080

DANN

Benign

0.40

DEOGEN2

Benign

0.022

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.011

M_CAP

Benign

0.035

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.34

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.43

N;N

REVEL

Benign

0.12

Sift

Benign

0.50

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.0010

B;B

Vest4

0.12

MutPred

0.24

Gain of glycosylation at T1117 (P = 0.0142);.;

MVP

0.14

MPC

0.067

ClinPred

0.015

GERP RS

-7.5

Varity_R

0.028

gMVP

0.040

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.0

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