Variant chr1-205921648-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_052934.4(SLC26A9):c.1973C>T(p.Pro658Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000504 in 1,608,386 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

SLC26A9
NM_052934.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.16

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC26A9	NM_052934.4 linkuse as main transcript	c.1973C>T	p.Pro658Leu	missense_variant	17/21	ENST00000367135.8	NP_443166.1
SLC26A9	NM_134325.3 linkuse as main transcript	c.1973C>T	p.Pro658Leu	missense_variant	17/22		NP_599152.2
SLC26A9	XM_011509121.3 linkuse as main transcript	c.1706C>T	p.Pro569Leu	missense_variant	16/20		XP_011507423.1
SLC26A9	XM_011509122.3 linkuse as main transcript	c.1481C>T	p.Pro494Leu	missense_variant	14/18		XP_011507424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A9	ENST00000367135.8 linkuse as main transcript	c.1973C>T	p.Pro658Leu	missense_variant	17/21	1	NM_052934.4	ENSP00000356103	P1	Q7LBE3-1
SLC26A9	ENST00000340781.8 linkuse as main transcript	c.1973C>T	p.Pro658Leu	missense_variant	16/21	1		ENSP00000341682		Q7LBE3-2
SLC26A9	ENST00000367134.2 linkuse as main transcript	c.1973C>T	p.Pro658Leu	missense_variant	17/22	5		ENSP00000356102		Q7LBE3-2
SLC26A9	ENST00000491127.5 linkuse as main transcript	n.1357C>T		non_coding_transcript_exon_variant	9/13	2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000544

AC:

AN:

238924

Hom.:

AF XY:

0.0000620

AC XY:

AN XY:

129062

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000179

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:

0.0000557

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.0000508

AC:

AN:

1456176

Hom.:

Cov.:

AF XY:

0.0000525

AC XY:

AN XY:

723804

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000136

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:

0.0000577

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000121

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

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

Mar 20, 2024

The c.1973C>T (p.P658L) alteration is located in exon 17 (coding exon 16) of the SLC26A9 gene. This alteration results from a C to T substitution at nucleotide position 1973, causing the proline (P) at amino acid position 658 to be replaced by a leucine (L). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.011

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.52

.;D;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.86

.;D;D

M_CAP

Uncertain

0.27

MetaRNN

Uncertain

0.62

D;D;D

MetaSVM

Uncertain

0.55

MutationAssessor

Uncertain

2.9

M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Uncertain

0.57

Sift

Uncertain

0.0030

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

.;D;.

Vest4

0.55

MVP

0.56

MPC

0.62

ClinPred

0.88

GERP RS

4.0

Varity_R

0.37

gMVP

0.88

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