rs55638457
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM1BP4_StrongBP6BS1BS2
The NM_000441.2(SLC26A4):āc.1790T>Cā(p.Leu597Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00837 in 1,598,500 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000441.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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SLC26A4 | ENST00000644269.2 | c.1790T>C | p.Leu597Ser | missense_variant | Exon 16 of 21 | NM_000441.2 | ENSP00000494017.1 | |||
SLC26A4 | ENST00000480841.5 | n.639T>C | non_coding_transcript_exon_variant | Exon 7 of 8 | 3 | |||||
SLC26A4 | ENST00000644846.1 | n.500T>C | non_coding_transcript_exon_variant | Exon 6 of 10 | ENSP00000494344.1 | |||||
SLC26A4 | ENST00000492030.2 | n.91-644T>C | intron_variant | Intron 1 of 5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00624 AC: 949AN: 152186Hom.: 7 Cov.: 32
GnomAD3 exomes AF: 0.00833 AC: 2092AN: 251102Hom.: 28 AF XY: 0.00982 AC XY: 1333AN XY: 135694
GnomAD4 exome AF: 0.00860 AC: 12437AN: 1446196Hom.: 118 Cov.: 27 AF XY: 0.00942 AC XY: 6786AN XY: 720586
GnomAD4 genome AF: 0.00623 AC: 949AN: 152304Hom.: 7 Cov.: 32 AF XY: 0.00639 AC XY: 476AN XY: 74462
ClinVar
Submissions by phenotype
not specified Benign:6
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p.Leu597Ser in exon 16 of SLC26A4: Although this variant has been reported in pa tients with Pendred syndrome and nonsyndromic hearing loss with enlarged vestibu lar aqueducts (EVA) (Campbell et al 2001, Fugazzola et al 2002, Blons 2004, Pryo r 2005), it has also been found in 2.7% (449/16590) of South Asian chromosomes b y the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs55638457). In addition, this variant has been identified by our laboratory in many individuals, none of whom had a pathogenic variant on the second allele. I n summary, this data meets our criteria to classify this variant as benign. -
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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not provided Benign:5
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SLC26A4: BS1, BS2 -
Pendred syndrome Benign:4
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
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Autosomal recessive nonsyndromic hearing loss 4 Uncertain:1Benign:1
This variant was classified as: Uncertain significance. -
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Pendred syndrome;C3538946:Autosomal recessive nonsyndromic hearing loss 4 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at