rs774353111
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_000441.2(SLC26A4):c.765+4A>C variant causes a splice donor region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,613,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
SLC26A4
NM_000441.2 splice_donor_region, intron
NM_000441.2 splice_donor_region, intron
Scores
1
1
Splicing: ADA: 0.9980
2
Clinical Significance
Conservation
PhyloP100: 8.79
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. Scorers claiming Uncertain: max_spliceai. No scorers claiming Benign.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A4 | NM_000441.2 | c.765+4A>C | splice_donor_region_variant, intron_variant | ENST00000644269.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A4 | ENST00000644269.2 | c.765+4A>C | splice_donor_region_variant, intron_variant | NM_000441.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000198 AC: 3AN: 151848Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000438 AC: 11AN: 251098Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135762
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GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461338Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23AN XY: 727020
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GnomAD4 genome ? AF: 0.0000198 AC: 3AN: 151848Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74150
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pendred syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Mar 20, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Splicing
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DL_spliceai
Position offset: -4
Find out detailed SpliceAI scores and Pangolin per-transcript scores at