chr11-118352416-C-T
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000073.3(CD3G):c.496C>T(p.Arg166Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,613,858 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 Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R166R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000073.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CD3G | NM_000073.3 | c.496C>T | p.Arg166Ter | stop_gained | 6/7 | ENST00000532917.3 | |
CD3G | XM_006718941.4 | c.496C>T | p.Arg166Ter | stop_gained | 6/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CD3G | ENST00000532917.3 | c.496C>T | p.Arg166Ter | stop_gained | 6/7 | 1 | NM_000073.3 | P1 | |
CD3G | ENST00000292144.8 | c.*553C>T | 3_prime_UTR_variant, NMD_transcript_variant | 7/8 | 1 | ||||
CD3G | ENST00000392883.6 | c.364C>T | p.Arg122Ter | stop_gained | 5/6 | 5 | |||
CD3G | ENST00000532903.1 | n.572C>T | non_coding_transcript_exon_variant | 7/8 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152088Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251462Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135902
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461652Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727156
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74432
ClinVar
Submissions by phenotype
Combined immunodeficiency due to CD3gamma deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 20, 2022 | This sequence change creates a premature translational stop signal (p.Arg166*) in the CD3G gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CD3G are known to be pathogenic (PMID: 1635567, 17277165, 24910257). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CD3G-related conditions. For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at