rs786204426
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PS1_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
NM_000441.2 start_lost
Scores
5
4
6
Clinical Significance
Conservation
PhyloP100: 3.97
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 13 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
PS1
?
Another start lost variant in NM_000441.2 (SLC26A4) was described as [Likely_pathogenic] in ClinVar as 188721
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A4 | NM_000441.2 | c.3G>A | p.Met1? | start_lost | 2/21 | ENST00000644269.2 | |
SLC26A4-AS1 | NR_028137.1 | n.155C>T | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A4 | ENST00000644269.2 | c.3G>A | p.Met1? | start_lost | 2/21 | NM_000441.2 | P1 | ||
SLC26A4-AS1 | ENST00000668981.1 | n.215C>T | non_coding_transcript_exon_variant | 1/2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1410240Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 698074
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1410240
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
698074
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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
Pathogenic, no assertion criteria provided | case-control | Deafness Molecular Diagnostic Center, Chinese PLA General Hospital | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D
PROVEAN
Benign
N;.;N
REVEL
Uncertain
Sift
Uncertain
D;.;D
Sift4G
Pathogenic
D;.;D
Polyphen
B;B;.
Vest4
MutPred
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
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.