Genetic Variant SLC26A9:p.Arg804Trp (chr1-205915146-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000340781.8(SLC26A9):c.2410A>T(p.Arg804Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R804G) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

SLC26A9
ENST00000340781.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.509

Publications

18 publications found

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 Gene-Disease associations (from GenCC):

cystic fibrosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC26A9 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09412363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A9	NM_052934.4 link	c.*211A>T		3_prime_UTR_variant	Exon 21 of 21	ENST00000367135.8	NP_443166.1	Q7LBE3-1
SLC26A9	NM_134325.3 link	c.2410A>T	p.Arg804Trp	missense_variant	Exon 22 of 22		NP_599152.2	Q7LBE3-2B3KXK1
SLC26A9	XM_011509121.3 link	c.*211A>T		3_prime_UTR_variant	Exon 20 of 20		XP_011507423.1
SLC26A9	XM_011509122.3 link	c.*211A>T		3_prime_UTR_variant	Exon 18 of 18		XP_011507424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC26A9	ENST00000340781.8 link	c.2410A>T	p.Arg804Trp	missense_variant	Exon 21 of 21	1		ENSP00000341682.4	Q7LBE3-2
SLC26A9	ENST00000367135.8 link	c.*211A>T		3_prime_UTR_variant	Exon 21 of 21	1	NM_052934.4	ENSP00000356103.3	Q7LBE3-1
SLC26A9	ENST00000367134.2 link	c.2410A>T	p.Arg804Trp	missense_variant	Exon 22 of 22	5		ENSP00000356102.2	Q7LBE3-2
SLC26A9	ENST00000491127.5 link	n.1971A>T		non_coding_transcript_exon_variant	Exon 13 of 13	2

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151840

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151840

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74148

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41264

American (AMR)

AF:

0.00

AC:

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67964

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.725

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

6162

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.26

CADD

Benign

8.9

(source)

DANN

Benign

0.97

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.60

.;T

M_CAP

Benign

0.057

MetaRNN

Benign

0.094

T;T

MetaSVM

Uncertain

-0.12

PhyloP100

0.51

PrimateAI

Benign

0.28

PROVEAN

Benign

0.020

N;N

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0090

D;D

Vest4

0.15

MutPred

0.32

Loss of disorder (P = 0.0094);Loss of disorder (P = 0.0094);

MVP

0.32

MPC

0.19

ClinPred

0.91

GERP RS

0.71

gMVP

0.17

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over