chr14-24631079-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004131.6(GZMB):c.736C>T(p.Arg246Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,612,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004131.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GZMB | NM_004131.6 | c.736C>T | p.Arg246Cys | missense_variant | 5/5 | ENST00000216341.9 | NP_004122.2 | |
GZMB | NM_001346011.2 | c.700C>T | p.Arg234Cys | missense_variant | 5/5 | NP_001332940.1 | ||
GZMB | NR_144343.2 | n.630C>T | non_coding_transcript_exon_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GZMB | ENST00000216341.9 | c.736C>T | p.Arg246Cys | missense_variant | 5/5 | 1 | NM_004131.6 | ENSP00000216341 | P2 | |
ENST00000555300.1 | n.177+7953G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152108Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251298Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135806
GnomAD4 exome AF: 0.0000390 AC: 57AN: 1460582Hom.: 0 Cov.: 30 AF XY: 0.0000399 AC XY: 29AN XY: 726736
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74298
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 06, 2022 | The c.736C>T (p.R246C) alteration is located in exon 5 (coding exon 5) of the GZMB gene. This alteration results from a C to T substitution at nucleotide position 736, causing the arginine (R) at amino acid position 246 to be replaced by a cysteine (C). 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