rs149454830
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_024753.5(TTC21B):āc.3416T>Cā(p.Val1139Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000465 in 1,613,918 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1139I) has been classified as Likely benign.
Frequency
Consequence
NM_024753.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTC21B | NM_024753.5 | c.3416T>C | p.Val1139Ala | missense_variant | 25/29 | ENST00000243344.8 | |
TTC21B | XM_017004967.2 | c.3416T>C | p.Val1139Ala | missense_variant | 25/28 | ||
TTC21B | XM_047445870.1 | c.2762T>C | p.Val921Ala | missense_variant | 21/25 | ||
TTC21B | XM_011511871.4 | c.2666T>C | p.Val889Ala | missense_variant | 20/24 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTC21B | ENST00000243344.8 | c.3416T>C | p.Val1139Ala | missense_variant | 25/29 | 1 | NM_024753.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00238 AC: 362AN: 152202Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000601 AC: 151AN: 251138Hom.: 2 AF XY: 0.000479 AC XY: 65AN XY: 135740
GnomAD4 exome AF: 0.000265 AC: 388AN: 1461598Hom.: 2 Cov.: 31 AF XY: 0.000234 AC XY: 170AN XY: 727104
GnomAD4 genome ? AF: 0.00238 AC: 363AN: 152320Hom.: 1 Cov.: 32 AF XY: 0.00240 AC XY: 179AN XY: 74484
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 16, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Sep 16, 2022 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 03, 2022 | The c.3416T>C (p.V1139A) alteration is located in exon 25 (coding exon 25) of the TTC21B gene. This alteration results from a T to C substitution at nucleotide position 3416, causing the valine (V) at amino acid position 1139 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Jeune thoracic dystrophy;C0687120:Nephronophthisis Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Feb 10, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at