14-24631084-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004131.6(GZMB):c.731T>A(p.Met244Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,230 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M244T) has been classified as Uncertain significance.
Frequency
Consequence
NM_004131.6 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GZMB | NM_004131.6 | c.731T>A | p.Met244Lys | missense_variant | 5/5 | ENST00000216341.9 | |
GZMB | NM_001346011.2 | c.695T>A | p.Met232Lys | missense_variant | 5/5 | ||
GZMB | NR_144343.2 | n.625T>A | non_coding_transcript_exon_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GZMB | ENST00000216341.9 | c.731T>A | p.Met244Lys | missense_variant | 5/5 | 1 | NM_004131.6 | P2 | |
ENST00000555300.1 | n.177+7958A>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152142Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251348Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135836
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1461088Hom.: 0 Cov.: 30 AF XY: 0.0000110 AC XY: 8AN XY: 726960
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74306
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 09, 2021 | The c.731T>A (p.M244K) alteration is located in exon 5 (coding exon 5) of the GZMB gene. This alteration results from a T to A substitution at nucleotide position 731, causing the methionine (M) at amino acid position 244 to be replaced by a lysine (K). 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