14-24607629-C-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The NM_033423.5(GZMH):c.322G>A(p.Asp108Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000254 in 1,612,504 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 Uncertain significance (★).
Frequency
Consequence
NM_033423.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GZMH | NM_033423.5 | c.322G>A | p.Asp108Asn | missense_variant | Exon 3 of 5 | ENST00000216338.9 | NP_219491.1 | |
GZMH | NM_001270780.2 | c.322G>A | p.Asp108Asn | missense_variant | Exon 3 of 5 | NP_001257709.1 | ||
GZMH | NM_001270781.2 | c.322G>A | p.Asp108Asn | missense_variant | Exon 3 of 4 | NP_001257710.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GZMH | ENST00000216338.9 | c.322G>A | p.Asp108Asn | missense_variant | Exon 3 of 5 | 1 | NM_033423.5 | ENSP00000216338.4 | ||
GZMH | ENST00000557220.6 | c.204+635G>A | intron_variant | Intron 2 of 2 | 1 | ENSP00000450576.2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000359 AC: 9AN: 251026Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135638
GnomAD4 exome AF: 0.0000260 AC: 38AN: 1460312Hom.: 0 Cov.: 36 AF XY: 0.0000262 AC XY: 19AN XY: 726484
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74336
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.322G>A (p.D108N) alteration is located in exon 3 (coding exon 3) of the GZMH gene. This alteration results from a G to A substitution at nucleotide position 322, causing the aspartic acid (D) at amino acid position 108 to be replaced by an asparagine (N). 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