14-24606610-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_033423.5(GZMH):c.734G>A(p.Arg245His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000825 in 1,612,872 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 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. R245C) has been classified as Likely benign.
Frequency
Consequence
NM_033423.5 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GZMH | NM_033423.5 | c.734G>A | p.Arg245His | missense_variant | Exon 5 of 5 | ENST00000216338.9 | NP_219491.1 | |
GZMH | NM_001270780.2 | c.542G>A | p.Arg181His | missense_variant | Exon 5 of 5 | NP_001257709.1 | ||
GZMH | NM_001270781.2 | c.476G>A | p.Arg159His | missense_variant | Exon 4 of 4 | NP_001257710.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GZMH | ENST00000216338.9 | c.734G>A | p.Arg245His | missense_variant | Exon 5 of 5 | 1 | NM_033423.5 | ENSP00000216338.4 | ||
GZMH | ENST00000557220.6 | c.341G>A | p.Arg114His | missense_variant | Exon 3 of 3 | 1 | ENSP00000450576.2 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000152 AC: 38AN: 249972Hom.: 1 AF XY: 0.000126 AC XY: 17AN XY: 135084
GnomAD4 exome AF: 0.0000815 AC: 119AN: 1460552Hom.: 1 Cov.: 31 AF XY: 0.0000881 AC XY: 64AN XY: 726656
GnomAD4 genome AF: 0.0000919 AC: 14AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74476
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.734G>A (p.R245H) alteration is located in exon 5 (coding exon 5) of the GZMH gene. This alteration results from a G to A substitution at nucleotide position 734, causing the arginine (R) at amino acid position 245 to be replaced by a histidine (H). 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