chr1-205920182-T-C

Position:

chr1-205920182-T-C

Variant summary

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

The NM_052934.4(SLC26A9):c.2104A>G(p.Ile702Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000824 in 1,613,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000090 ( 0 hom. )

Consequence

SLC26A9
NM_052934.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.29

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15699264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC26A9	NM_052934.4 linkuse as main transcript	c.2104A>G	p.Ile702Val	missense_variant	18/21	ENST00000367135.8	NP_443166.1
SLC26A9	NM_134325.3 linkuse as main transcript	c.2104A>G	p.Ile702Val	missense_variant	18/22		NP_599152.2
SLC26A9	XM_011509121.3 linkuse as main transcript	c.1837A>G	p.Ile613Val	missense_variant	17/20		XP_011507423.1
SLC26A9	XM_011509122.3 linkuse as main transcript	c.1612A>G	p.Ile538Val	missense_variant	15/18		XP_011507424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A9	ENST00000367135.8 linkuse as main transcript	c.2104A>G	p.Ile702Val	missense_variant	18/21	1	NM_052934.4	ENSP00000356103	P1	Q7LBE3-1
SLC26A9	ENST00000340781.8 linkuse as main transcript	c.2104A>G	p.Ile702Val	missense_variant	17/21	1		ENSP00000341682		Q7LBE3-2
SLC26A9	ENST00000367134.2 linkuse as main transcript	c.2104A>G	p.Ile702Val	missense_variant	18/22	5		ENSP00000356102		Q7LBE3-2
SLC26A9	ENST00000491127.5 linkuse as main transcript	n.1488A>G		non_coding_transcript_exon_variant	10/13	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000278

AC:

AN:

251490

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000123

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:

0.0000439

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000896

AC:

131

AN:

1461640

Hom.:

Cov.:

AF XY:

0.0000770

AC XY:

AN XY:

727118

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:

0.000116

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 10, 2022

The c.2104A>G (p.I702V) alteration is located in exon 18 (coding exon 17) of the SLC26A9 gene. This alteration results from a A to G substitution at nucleotide position 2104, causing the isoleucine (I) at amino acid position 702 to be replaced by a valine (V). 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

0.095

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.15

.;T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.071

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.73

.;T;T

M_CAP

Benign

0.041

MetaRNN

Benign

0.16

T;T;T

MetaSVM

Benign

-0.56

MutationAssessor

Benign

1.0

L;L;L

MutationTaster

Benign

0.95

N;N;N

PrimateAI

Benign

0.47

PROVEAN

Benign

0.060

N;N;N

REVEL

Benign

0.23

Sift

Benign

0.16

T;T;T

Sift4G

Benign

0.56

T;T;T

Polyphen

0.0010

.;B;.

Vest4

0.10

MutPred

0.67

Gain of phosphorylation at Y707 (P = 0.177);Gain of phosphorylation at Y707 (P = 0.177);Gain of phosphorylation at Y707 (P = 0.177);

MVP

0.39

MPC

0.12

ClinPred

0.065

GERP RS

4.3

Varity_R

0.12

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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