rs111033193
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_000441.2(SLC26A4):c.1614C>T(p.Asn538=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000135 in 1,591,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★★).
Frequency
Consequence
NM_000441.2 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A4 | NM_000441.2 | c.1614C>T | p.Asn538= | splice_region_variant, synonymous_variant | 14/21 | ENST00000644269.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A4 | ENST00000644269.2 | c.1614C>T | p.Asn538= | splice_region_variant, synonymous_variant | 14/21 | NM_000441.2 | P1 | ||
SLC26A4 | ENST00000477350.5 | n.461C>T | splice_region_variant, non_coding_transcript_exon_variant | 4/5 | 4 | ||||
SLC26A4 | ENST00000480841.5 | n.463C>T | splice_region_variant, non_coding_transcript_exon_variant | 5/8 | 3 | ||||
SLC26A4 | ENST00000644846.1 | c.327C>T | p.Asn109= | splice_region_variant, synonymous_variant, NMD_transcript_variant | 4/10 |
Frequencies
GnomAD3 genomes ? AF: 0.000631 AC: 96AN: 152088Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000215 AC: 54AN: 251058Hom.: 0 AF XY: 0.000147 AC XY: 20AN XY: 135686
GnomAD4 exome AF: 0.0000827 AC: 119AN: 1439706Hom.: 0 Cov.: 26 AF XY: 0.0000669 AC XY: 48AN XY: 717756
GnomAD4 genome ? AF: 0.000631 AC: 96AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.000564 AC XY: 42AN XY: 74432
ClinVar
Submissions by phenotype
Pendred syndrome Uncertain:1Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Dec 28, 2017 | - - |
Likely benign, reviewed by expert panel | curation | ClinGen Hearing Loss Variant Curation Expert Panel | Jul 29, 2019 | The SLC26A4 p.Asn538Asn variant has been reported in the heterozygous state in one individual with unilateral hearing loss (PMID: 20621367). However, this variant is synonymous and is not predicted by computational prediction analysis, using MaxEntScan, to impact splicing (BP4, BP7). The filtering allele frequency (the lower threshold of the 95% CI of 60/24964) of the p.Asn538Asn variant in SLC26A4 is 0.19168% for African chromosomes in gnomAD, which is a higher frequency than would be expected for an autosomal recessive pathogenic variant based on the thresholds defined by the ClinGen Hearing Loss Expert Panel (BS1_Supporting; http://gnomad.broadinstitute.org). This variant has also been reported in ClinVar (Variation ID 43517). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BS1_Supporting, BP4, BP7. - |
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Jan 16, 2020 | - - |
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 23, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 04, 2020 | This variant is associated with the following publications: (PMID: 30245029, 20621367) - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 01, 2008 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at