Variant rs786204831 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PP2PP3_StrongPP5_Moderate

The NM_003047.5(SLC9A1):c.913G>A(p.Gly305Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC9A1
NM_003047.5 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 7.90

Variant links:

Genes affected

SLC9A1 (HGNC:11071): (solute carrier family 9 member A1) This gene encodes a Na+/H+ antiporter that is a member of the solute carrier family 9. The encoded protein is a plasma membrane transporter that is expressed in the kidney and intestine. This protein plays a central role in regulating pH homeostasis, cell migration and cell volume. This protein may also be involved in tumor growth. [provided by RefSeq, Sep 2011]

SLC9A1 links:

SLC9A1 (HGNC:):

SLC9A1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SLC9A1. . Gene score misZ 3.5504 (greater than the threshold 3.09). Trascript score misZ 4.6807 (greater than threshold 3.09). GenCC has associacion of gene with Lichtenstein-Knorr syndrome.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.989

PP5

Variant 1-27109678-C-T is Pathogenic according to our data. Variant chr1-27109678-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 189315.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-27109678-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A1	NM_003047.5 linkuse as main transcript	c.913G>A	p.Gly305Arg	missense_variant	3/12	ENST00000263980.8	NP_003038.2	P19634-1B2RAH2
SLC9A1	XM_011542021.4 linkuse as main transcript	c.583G>A	p.Gly195Arg	missense_variant	4/13		XP_011540323.1
SLC9A1	XM_047428769.1 linkuse as main transcript	c.583G>A	p.Gly195Arg	missense_variant	7/16		XP_047284725.1
SLC9A1	NR_046474.2 linkuse as main transcript	n.1243G>A		non_coding_transcript_exon_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC9A1	ENST00000263980.8 linkuse as main transcript	c.913G>A	p.Gly305Arg	missense_variant	3/12	1	NM_003047.5	ENSP00000263980.3		P19634-1
SLC9A1	ENST00000374086.3 linkuse as main transcript	c.913G>A	p.Gly305Arg	missense_variant	3/5	1		ENSP00000363199.3		P19634-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461658

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727122

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

GeneDx

May 21, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25205112) -

Lichtenstein-Knorr syndrome

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 15, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.48

T;.

Eigen

Pathogenic

1.1

Eigen_PC

Pathogenic

0.99

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

1.0

D;D

M_CAP

Pathogenic

0.46

MetaRNN

Pathogenic

0.99

D;D

MetaSVM

Benign

-0.47

MutationAssessor

Pathogenic

3.8

H;H

PrimateAI

Uncertain

0.76

PROVEAN

Pathogenic

-7.3

D;D

REVEL

Pathogenic

0.94

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.99

MutPred

0.91

Gain of methylation at G305 (P = 0.0053);Gain of methylation at G305 (P = 0.0053);

MVP

0.65

MPC

2.3

ClinPred

1.0

GERP RS

6.0

Varity_R

0.97

gMVP

0.99

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

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