rs1294549037
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_024753.5(TTC21B):c.3713G>A(p.Gly1238Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,576 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G1238G) has been classified as Likely benign.
Frequency
Consequence
NM_024753.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC21B | NM_024753.5 | c.3713G>A | p.Gly1238Glu | missense_variant | 27/29 | ENST00000243344.8 | |
TTC21B | XM_017004967.2 | c.3713G>A | p.Gly1238Glu | missense_variant | 27/28 | ||
TTC21B | XM_047445870.1 | c.3059G>A | p.Gly1020Glu | missense_variant | 23/25 | ||
TTC21B | XM_011511871.4 | c.2963G>A | p.Gly988Glu | missense_variant | 22/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC21B | ENST00000243344.8 | c.3713G>A | p.Gly1238Glu | missense_variant | 27/29 | 1 | NM_024753.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460576Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726636
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Asphyxiating thoracic dystrophy 4;C3151186:Nephronophthisis 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | May 17, 2022 | - - |
Nephronophthisis 12 Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | Jun 26, 2017 | This missense variant G1238E is absent from gnomAD and is found in trans to a pathogenic variant (P209L) and is predicted to be damaging. (PM2, PM3, PP3) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at