7-107710150-T-C
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PM1PM2PP3PP5_Very_Strong
The NM_000441.2(SLC26A4):c.2186T>C(p.Leu729Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000823 in 1,457,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. L729L) has been classified as Likely benign.
Frequency
Consequence
NM_000441.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC26A4 | NM_000441.2 | c.2186T>C | p.Leu729Pro | missense_variant | 19/21 | ENST00000644269.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC26A4 | ENST00000644269.2 | c.2186T>C | p.Leu729Pro | missense_variant | 19/21 | NM_000441.2 | P1 | ||
SLC26A4 | ENST00000644846.1 | c.*88T>C | 3_prime_UTR_variant, NMD_transcript_variant | 8/10 | |||||
SLC26A4 | ENST00000492030.2 | n.377-5T>C | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000823 AC: 12AN: 1457378Hom.: 0 Cov.: 27 AF XY: 0.00000965 AC XY: 7AN XY: 725312
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Pendred syndrome Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Jun 12, 2017 | - - |
Likely pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Mar 20, 2021 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2023 | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC26A4 protein function. ClinVar contains an entry for this variant (Variation ID: 552468). This missense change has been observed in individuals with SLC26A4-related conditions (PMID: 20146813, 23336812, 23401162, 25394566). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 729 of the SLC26A4 protein (p.Leu729Pro). - |
Autosomal recessive nonsyndromic hearing loss 4 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 31, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at