Variant 7-107661644-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_ModeratePS1_ModeratePM2PP5

The NM_000441.2(SLC26A4):c.3G>A(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC26A4
NM_000441.2 start_lost

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 3.97

Variant links:

Genes affected

SLC26A4 (HGNC:8818): (solute carrier family 26 member 4) Mutations in this gene are associated with Pendred syndrome, the most common form of syndromic deafness, an autosomal-recessive disease. It is highly homologous to the SLC26A3 gene; they have similar genomic structures and this gene is located 3' of the SLC26A3 gene. The encoded protein has homology to sulfate transporters. [provided by RefSeq, Jul 2008]

SLC26A4 links:

SLC26A4-AS1 (HGNC:22385): (SLC26A4 antisense RNA 1)

SLC26A4-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PVS1

Start lost variant, next in-frame start position is after 1 pathogenic variants. Next in-frame start position is after 60 CDS bases. Genomic position: 107661701. Lost 0.026 part of the original CDS.

PS1

Another start lost variant in NM_000441.2 (SLC26A4) was described as [Pathogenic] in Lovd

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 7-107661644-G-A is Pathogenic according to our data. Variant chr7-107661644-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 1185667.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A4	NM_000441.2 link	c.3G>A	p.Met1?	start_lost	Exon 2 of 21	ENST00000644269.2	NP_000432.1	O43511-1
SLC26A4-AS1	NR_028137.1 link	n.155C>T		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A4	ENST00000644269.2 link	c.3G>A	p.Met1?	start_lost	Exon 2 of 21		NM_000441.2	ENSP00000494017.1		O43511-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1410240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

698074

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Autosomal recessive nonsyndromic hearing loss 4

Pathogenic:1

Deafness Molecular Diagnostic Center, Chinese PLA General Hospital

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: case-control

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Pathogenic

0.37

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.085

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.90

.;D;D

M_CAP

Pathogenic

0.90

MetaRNN

Pathogenic

0.98

D;D;D

MetaSVM

Uncertain

0.0016

PROVEAN

Benign

-0.92

N;.;N

REVEL

Uncertain

0.56

Sift

Uncertain

0.026

D;.;D

Sift4G

Pathogenic

0.0

D;.;D

Polyphen

0.020

B;B;.

Vest4

0.90

MutPred

1.0

Loss of glycosylation at P4 (P = 0.4565);Loss of glycosylation at P4 (P = 0.4565);Loss of glycosylation at P4 (P = 0.4565);

MVP

0.85

ClinPred

0.99

GERP RS

3.8

Varity_R

0.47

gMVP

0.43

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over