Variant rs745927136 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003047.5(SLC9A1):c.1585C>T(p.His529Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,328 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SLC9A1
NM_003047.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 9.95

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC9A1	NM_003047.5 link	c.1585C>T	p.His529Tyr	missense_variant	7/12	ENST00000263980.8	NP_003038.2	P19634-1B2RAH2
SLC9A1	XM_011542021.4 link	c.1255C>T	p.His419Tyr	missense_variant	8/13		XP_011540323.1
SLC9A1	XM_047428769.1 link	c.1255C>T	p.His419Tyr	missense_variant	11/16		XP_047284725.1
SLC9A1	NR_046474.2 link	n.1915C>T		non_coding_transcript_exon_variant	6/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC9A1	ENST00000263980.8 link	c.1585C>T	p.His529Tyr	missense_variant	7/12	1	NM_003047.5	ENSP00000263980.3	P19634-1
SLC9A1	ENST00000374089.5 link	n.810C>T		non_coding_transcript_exon_variant	2/7	2
SLC9A1	ENST00000447808.1 link	n.62C>T		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000400

AC:

AN:

250210

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135468

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461328

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000336

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 02, 2015

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 31, 2022

This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 529 of the SLC9A1 protein (p.His529Tyr). This variant is present in population databases (rs745927136, gnomAD 0.03%). This missense change has been observed in individual(s) with a neuromuscular disorder (PMID: 30018422). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.84

Eigen

Uncertain

0.57

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.64

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.0

PrimateAI

Pathogenic

0.89

PROVEAN

Pathogenic

-5.8

REVEL

Uncertain

0.47

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.028

Polyphen

0.90

Vest4

0.74

MutPred

0.56

Loss of catalytic residue at L531 (P = 0.0596);

MVP

0.51

MPC

2.3

ClinPred

0.63

GERP RS

4.6

Varity_R

0.86

gMVP

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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