1-205921587-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_052934.4(SLC26A9):c.2034G>A(p.Met678Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000054 in 1,610,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00036 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

SLC26A9
NM_052934.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64

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 Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36929724).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC26A9	NM_052934.4 linkuse as main transcript	c.2034G>A	p.Met678Ile	missense_variant	17/21	ENST00000367135.8
SLC26A9	NM_134325.3 linkuse as main transcript	c.2034G>A	p.Met678Ile	missense_variant	17/22
SLC26A9	XM_011509121.3 linkuse as main transcript	c.1767G>A	p.Met589Ile	missense_variant	16/20
SLC26A9	XM_011509122.3 linkuse as main transcript	c.1542G>A	p.Met514Ile	missense_variant	14/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC26A9	ENST00000367135.8 linkuse as main transcript	c.2034G>A	p.Met678Ile	missense_variant	17/21	1	NM_052934.4	P1	Q7LBE3-1
SLC26A9	ENST00000340781.8 linkuse as main transcript	c.2034G>A	p.Met678Ile	missense_variant	16/21	1			Q7LBE3-2
SLC26A9	ENST00000367134.2 linkuse as main transcript	c.2034G>A	p.Met678Ile	missense_variant	17/22	5			Q7LBE3-2
SLC26A9	ENST00000491127.5 linkuse as main transcript	n.1418G>A		non_coding_transcript_exon_variant	9/13	2

Frequencies

GnomAD3 genomes

AF:

0.000361

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000110

AC:

AN:

245396

Hom.:

AF XY:

0.0000678

AC XY:

AN XY:

132782

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000786

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:

0.0000219

AC:

AN:

1457982

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

725112

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000717

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:

0.00

GnomAD4 genome

AF:

0.000361

AC:

AN:

152172

Hom.:

Cov.:

AF XY:

0.000592

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00360

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000332

ExAC

AF:

0.00000824

AC:

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

Feb 28, 2023

The c.2034G>A (p.M678I) alteration is located in exon 17 (coding exon 16) of the SLC26A9 gene. This alteration results from a G to A substitution at nucleotide position 2034, causing the methionine (M) at amino acid position 678 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

Pathogenic

0.94

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.10

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.061

MetaRNN

Benign

0.37

T;T;T

MetaSVM

Uncertain

0.43

MutationAssessor

Uncertain

2.4

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.54

N;N;N

REVEL

Uncertain

0.49

Sift

Uncertain

0.0060

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.27

.;B;.

Vest4

0.76

MutPred

0.69

Gain of catalytic residue at L683 (P = 0.034);Gain of catalytic residue at L683 (P = 0.034);Gain of catalytic residue at L683 (P = 0.034);

MVP

0.59

MPC

0.38

ClinPred

0.23

GERP RS

4.4

Varity_R

0.74

gMVP

0.80

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