1-205915074-A-G

Position:

chr1-205915074-A-G

Variant summary

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

The NM_134325.3(SLC26A9):c.2482T>C(p.Ser828Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,613,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00033 ( 0 hom. )

Consequence

SLC26A9
NM_134325.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.211

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 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=0.050245225).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A9	NM_052934.4 linkuse as main transcript	c.*283T>C		3_prime_UTR_variant	21/21	ENST00000367135.8	NP_443166.1	Q7LBE3-1
SLC26A9	NM_134325.3 linkuse as main transcript	c.2482T>C	p.Ser828Pro	missense_variant	22/22		NP_599152.2	Q7LBE3-2B3KXK1
SLC26A9	XM_011509121.3 linkuse as main transcript	c.*283T>C		3_prime_UTR_variant	20/20		XP_011507423.1
SLC26A9	XM_011509122.3 linkuse as main transcript	c.*283T>C		3_prime_UTR_variant	18/18		XP_011507424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC26A9	ENST00000340781.8 linkuse as main transcript	c.2482T>C	p.Ser828Pro	missense_variant	21/21	1		ENSP00000341682.4	Q7LBE3-2
SLC26A9	ENST00000367135 linkuse as main transcript	c.*283T>C		3_prime_UTR_variant	21/21	1	NM_052934.4	ENSP00000356103.3	Q7LBE3-1
SLC26A9	ENST00000367134.2 linkuse as main transcript	c.2482T>C	p.Ser828Pro	missense_variant	22/22	5		ENSP00000356102.2	Q7LBE3-2
SLC26A9	ENST00000491127.5 linkuse as main transcript	n.2043T>C		non_coding_transcript_exon_variant	13/13	2

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000796

AC:

AN:

251276

Hom.:

AF XY:

0.0000884

AC XY:

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

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:

0.000167

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000332

AC:

486

AN:

1461836

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

232

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

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:

0.000428

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000125

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000818

Hom.:

Bravo

AF:

0.000125

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.0000906

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000237

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 31, 2024

The c.2482T>C (p.S828P) alteration is located in exon 22 (coding exon 21) of the SLC26A9 gene. This alteration results from a T to C substitution at nucleotide position 2482, causing the serine (S) at amino acid position 828 to be replaced by a proline (P). 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

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.43

CADD

Benign

3.8

DANN

Benign

0.87

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.31

.;T

M_CAP

Benign

0.061

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-0.34

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.030

N;N

REVEL

Benign

0.20

Sift

Uncertain

0.021

D;D

Sift4G

Benign

0.35

T;T

Vest4

0.053

MVP

0.099

MPC

0.17

ClinPred

0.14

GERP RS

-5.7

gMVP

0.023

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