1-205918920-C-T

Position:

chr1-205918920-C-T

Variant summary

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

The NM_052934.4(SLC26A9):c.2176G>A(p.Val726Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 1,614,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000092 ( 0 hom. )

Consequence

SLC26A9
NM_052934.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.563

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 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=0.0582411).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC26A9	NM_052934.4 linkuse as main transcript	c.2176G>A	p.Val726Ile	missense_variant	19/21	ENST00000367135.8	NP_443166.1
SLC26A9	NM_134325.3 linkuse as main transcript	c.2176G>A	p.Val726Ile	missense_variant	19/22		NP_599152.2
SLC26A9	XM_011509121.3 linkuse as main transcript	c.1909G>A	p.Val637Ile	missense_variant	18/20		XP_011507423.1
SLC26A9	XM_011509122.3 linkuse as main transcript	c.1684G>A	p.Val562Ile	missense_variant	16/18		XP_011507424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A9	ENST00000367135.8 linkuse as main transcript	c.2176G>A	p.Val726Ile	missense_variant	19/21	1	NM_052934.4	ENSP00000356103	P1	Q7LBE3-1
SLC26A9	ENST00000340781.8 linkuse as main transcript	c.2176G>A	p.Val726Ile	missense_variant	18/21	1		ENSP00000341682		Q7LBE3-2
SLC26A9	ENST00000367134.2 linkuse as main transcript	c.2176G>A	p.Val726Ile	missense_variant	19/22	5		ENSP00000356102		Q7LBE3-2
SLC26A9	ENST00000491127.5 linkuse as main transcript	n.1560G>A		non_coding_transcript_exon_variant	11/13	2

Frequencies

GnomAD3 genomes

AF:

0.0000985

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000139

AC:

AN:

251472

Hom.:

AF XY:

0.000132

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000370

Gnomad NFE exome

AF:

0.000149

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000917

AC:

134

AN:

1461880

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.000655

Gnomad4 NFE exome

AF:

0.0000612

Gnomad4 OTH exome

AF:

0.0000993

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000143

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000178

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

Mar 17, 2023

The c.2176G>A (p.V726I) alteration is located in exon 19 (coding exon 18) of the SLC26A9 gene. This alteration results from a G to A substitution at nucleotide position 2176, causing the valine (V) at amino acid position 726 to be replaced by an isoleucine (I). 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

0.073

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.36

CADD

Benign

8.4

DANN

Benign

0.96

DEOGEN2

Benign

0.10

.;T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.65

.;T;T

M_CAP

Benign

0.049

MetaRNN

Benign

0.058

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

-0.52

N;N;N

MutationTaster

Benign

0.93

N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.61

N;N;N

REVEL

Benign

0.13

Sift

Benign

0.19

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010

.;B;.

Vest4

0.054

MVP

0.34

MPC

0.11

ClinPred

0.062

GERP RS

-0.39

Varity_R

0.085

gMVP

0.12

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