20-1181414-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001304748.2(TMEM74B):c.205C>T(p.His69Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,526,878 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 (★).
Frequency
Consequence
NM_001304748.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM74B | NM_001304748.2 | c.205C>T | p.His69Tyr | missense_variant | 3/3 | ENST00000429036.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM74B | ENST00000429036.2 | c.205C>T | p.His69Tyr | missense_variant | 3/3 | 3 | NM_001304748.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000488 AC: 9AN: 184524Hom.: 0 AF XY: 0.0000515 AC XY: 5AN XY: 97052
GnomAD4 exome AF: 0.0000327 AC: 45AN: 1374710Hom.: 0 Cov.: 31 AF XY: 0.0000282 AC XY: 19AN XY: 673966
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74328
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 17, 2023 | The c.205C>T (p.H69Y) alteration is located in exon 2 (coding exon 2) of the TMEM74B gene. This alteration results from a C to T substitution at nucleotide position 205, causing the histidine (H) at amino acid position 69 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at