NM_000441.2:c.2000T>G
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PM1PM2PM5PP2PP3_StrongPP5
The NM_000441.2(SLC26A4):c.2000T>G(p.Phe667Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F667S) has been classified as Uncertain significance.
Frequency
Consequence
NM_000441.2 missense
Scores
Clinical Significance
Conservation
Publications
- autosomal recessive nonsyndromic hearing loss 4Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
- Pendred syndromeInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen
- athyreosisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- thyroid hypoplasiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- hearing loss, autosomal recessiveInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Pathogenic. The variant received 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SLC26A4 | ENST00000644269.2 | c.2000T>G | p.Phe667Cys | missense_variant | Exon 17 of 21 | NM_000441.2 | ENSP00000494017.1 | |||
SLC26A4 | ENST00000492030.2 | n.287T>G | non_coding_transcript_exon_variant | Exon 2 of 6 | 5 | |||||
SLC26A4 | ENST00000644846.1 | n.710T>G | non_coding_transcript_exon_variant | Exon 7 of 10 | ENSP00000494344.1 | |||||
SLC26A4 | ENST00000480841.5 | n.*139T>G | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Pendred syndrome Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at