1-205915365-C-T

Position:

chr1-205915365-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052934.4(SLC26A9):c.2368G>A(p.Ala790Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000397 in 1,614,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

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

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

SLC26A9
NM_052934.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.20

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:

SLC26A9 (HGNC:):

SLC26A9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26178688).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A9	NM_052934.4 linkuse as main transcript	c.2368G>A	p.Ala790Thr	missense_variant	21/21	ENST00000367135.8	NP_443166.1	Q7LBE3-1
SLC26A9	NM_134325.3 linkuse as main transcript	c.2368G>A	p.Ala790Thr	missense_variant	21/22		NP_599152.2	Q7LBE3-2B3KXK1
SLC26A9	XM_011509121.3 linkuse as main transcript	c.2101G>A	p.Ala701Thr	missense_variant	20/20		XP_011507423.1
SLC26A9	XM_011509122.3 linkuse as main transcript	c.1876G>A	p.Ala626Thr	missense_variant	18/18		XP_011507424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC26A9	ENST00000367135.8 linkuse as main transcript	c.2368G>A	p.Ala790Thr	missense_variant	21/21	1	NM_052934.4	ENSP00000356103.3	Q7LBE3-1
SLC26A9	ENST00000340781.8 linkuse as main transcript	c.2368G>A	p.Ala790Thr	missense_variant	20/21	1		ENSP00000341682.4	Q7LBE3-2
SLC26A9	ENST00000367134.2 linkuse as main transcript	c.2368G>A	p.Ala790Thr	missense_variant	21/22	5		ENSP00000356102.2	Q7LBE3-2
SLC26A9	ENST00000491127.5 linkuse as main transcript	n.1752G>A		non_coding_transcript_exon_variant	13/13	2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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:

0.0000485

AC:

AN:

247616

Hom.:

AF XY:

0.0000522

AC XY:

AN XY:

134048

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000908

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.0000383

AC:

AN:

1461822

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000809

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jul 22, 2024

The c.2368G>A (p.A790T) alteration is located in exon 21 (coding exon 20) of the SLC26A9 gene. This alteration results from a G to A substitution at nucleotide position 2368, causing the alanine (A) at amino acid position 790 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

0.13

BayesDel_addAF

Benign

-0.0016

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.055

.;T;.

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.54

.;T;T

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Uncertain

0.73

MutationAssessor

Benign

0.90

L;L;L

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.59

N;N;N

REVEL

Uncertain

0.37

Sift

Uncertain

0.0060

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.64

MVP

0.58

MPC

0.51

ClinPred

0.27

GERP RS

5.4

Varity_R

0.22

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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