NM_052934.4:c.2243A>G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_052934.4(SLC26A9):c.2243A>G(p.His748Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0788 in 1,612,986 control chromosomes in the GnomAD database, including 5,749 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.099 ( 920 hom., cov: 33)

Exomes 𝑓: 0.077 ( 4829 hom. )

Consequence

SLC26A9
NM_052934.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.93

Variant links:

Genes affected

SLC26A9 (HGNC:14469): (solute carrier family 26 member 9) This gene is one member of a family of sulfate/anion transporter genes. Family members are well conserved in their genomic (number and size of exons) and protein (aa length among species) structures yet have markedly different tissue expression patterns. The product of this gene is a highly selective chloride ion channel regulated by WNK kinases. Alternative splicing results in multiple transcript variants encoding differing isoforms.[provided by RefSeq, Dec 2008]

SLC26A9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014667511).

BP6

Variant 1-205918853-T-C is Benign according to our data. Variant chr1-205918853-T-C is described in ClinVar as [Benign]. Clinvar id is 403452.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A9	NM_052934.4 link	c.2243A>G	p.His748Arg	missense_variant	Exon 19 of 21	ENST00000367135.8	NP_443166.1	Q7LBE3-1
SLC26A9	NM_134325.3 link	c.2243A>G	p.His748Arg	missense_variant	Exon 19 of 22		NP_599152.2	Q7LBE3-2B3KXK1
SLC26A9	XM_011509121.3 link	c.1976A>G	p.His659Arg	missense_variant	Exon 18 of 20		XP_011507423.1
SLC26A9	XM_011509122.3 link	c.1751A>G	p.His584Arg	missense_variant	Exon 16 of 18		XP_011507424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC26A9	ENST00000367135.8 link	c.2243A>G	p.His748Arg	missense_variant	Exon 19 of 21	1	NM_052934.4	ENSP00000356103.3	Q7LBE3-1
SLC26A9	ENST00000340781.8 link	c.2243A>G	p.His748Arg	missense_variant	Exon 18 of 21	1		ENSP00000341682.4	Q7LBE3-2
SLC26A9	ENST00000367134.2 link	c.2243A>G	p.His748Arg	missense_variant	Exon 19 of 22	5		ENSP00000356102.2	Q7LBE3-2
SLC26A9	ENST00000491127.5 link	n.1627A>G		non_coding_transcript_exon_variant	Exon 11 of 13	2

Frequencies

GnomAD3 genomes

AF:

0.0989

AC:

15044

AN:

152108

Hom.:

916

Cov.:

show subpopulations

Gnomad AFR

AF:

0.169

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.0753

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0325

Gnomad FIN

AF:

0.0430

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0803

Gnomad OTH

AF:

0.115

GnomAD3 exomes

AF:

0.0718

AC:

18044

AN:

251402

Hom.:

882

AF XY:

0.0700

AC XY:

9512

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.0502

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0326

Gnomad FIN exome

AF:

0.0467

Gnomad NFE exome

AF:

0.0839

Gnomad OTH exome

AF:

0.0859

GnomAD4 exome

AF:

0.0767

AC:

111996

AN:

1460760

Hom.:

4829

Cov.:

AF XY:

0.0758

AC XY:

55073

AN XY:

726544

show subpopulations

Gnomad4 AFR exome

AF:

0.174

Gnomad4 AMR exome

AF:

0.0527

Gnomad4 ASJ exome

AF:

0.133

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0325

Gnomad4 FIN exome

AF:

0.0478

Gnomad4 NFE exome

AF:

0.0802

Gnomad4 OTH exome

AF:

0.0828

GnomAD4 genome

AF:

0.0990

AC:

15067

AN:

152226

Hom.:

920

Cov.:

AF XY:

0.0946

AC XY:

7039

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.169

Gnomad4 AMR

AF:

0.0751

Gnomad4 ASJ

AF:

0.136

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0323

Gnomad4 FIN

AF:

0.0430

Gnomad4 NFE

AF:

0.0803

Gnomad4 OTH

AF:

0.114

Alfa

AF:

0.0884

Hom.:

1565

Bravo

AF:

0.106

TwinsUK

AF:

0.0806

AC:

299

ALSPAC

AF:

0.0781

AC:

301

ESP6500AA

AF:

0.168

AC:

740

ESP6500EA

AF:

0.0840

AC:

722

ExAC

AF:

0.0742

AC:

9010

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.0930

EpiControl

AF:

0.0937

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.0010

DANN

Benign

0.25

DEOGEN2

Benign

0.032

.;T;.

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.33

.;T;T

MetaRNN

Benign

0.0015

T;T;T

MetaSVM

Benign

-0.74

MutationAssessor

Benign

0.20

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.11

N;N;N

REVEL

Benign

0.26

Sift

Benign

0.66

T;T;T

Sift4G

Benign

0.92

T;T;T

Polyphen

0.0

.;B;.

Vest4

0.011

MPC

0.17

ClinPred

0.0041

GERP RS

-10

Varity_R

0.021

gMVP

0.18

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