rs727504813
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000441.2(SLC26A4):āc.2242C>Gā(p.Leu748Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,546,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_000441.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A4 | NM_000441.2 | c.2242C>G | p.Leu748Val | missense_variant | 20/21 | ENST00000644269.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A4 | ENST00000644269.2 | c.2242C>G | p.Leu748Val | missense_variant | 20/21 | NM_000441.2 | P1 | ||
SLC26A4 | ENST00000492030.2 | n.428C>G | non_coding_transcript_exon_variant | 5/6 | 5 | ||||
SLC26A4 | ENST00000644846.1 | c.*144C>G | 3_prime_UTR_variant, NMD_transcript_variant | 9/10 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251220Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135790
GnomAD4 exome AF: 0.00000789 AC: 11AN: 1394410Hom.: 0 Cov.: 25 AF XY: 0.0000100 AC XY: 7AN XY: 697734
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152146Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74314
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 13, 2013 | The Leu748Val variant in SLC26A4 has not been previously reported in individuals with hearing loss or in large population studies. Computational tools (amino a cid biochemical properties, conservation, SIFT, AlignGVGD, PolyPhen-2) suggest t hat this variant may not impact the protein, though this information is not pred ictive enough to rule out pathogenicity. In summary, additional information is n eeded to determine the clinical significance of this variant. - |
Pendred syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at