11-65116486-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_014205.4(ZNHIT2):c.1168G>A(p.Val390Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000705 in 1,518,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. V390L) has been classified as Likely benign.
Frequency
Consequence
NM_014205.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ZNHIT2 | ENST00000310597.6 | c.1168G>A | p.Val390Met | missense_variant | Exon 1 of 1 | 6 | NM_014205.4 | ENSP00000308548.4 | ||
ZNHIT2 | ENST00000528598.1 | c.*114G>A | downstream_gene_variant | 3 | ENSP00000436896.1 | |||||
TM7SF2 | ENST00000529292.5 | n.*983C>T | downstream_gene_variant | 5 | ENSP00000436370.1 | |||||
TM7SF2 | ENST00000529601.5 | n.*1365C>T | downstream_gene_variant | 2 | ENSP00000435458.1 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152224Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000122 AC: 22AN: 179752Hom.: 0 AF XY: 0.000137 AC XY: 13AN XY: 94662
GnomAD4 exome AF: 0.0000710 AC: 97AN: 1365878Hom.: 0 Cov.: 70 AF XY: 0.0000942 AC XY: 63AN XY: 668484
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152224Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74376
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1168G>A (p.V390M) alteration is located in exon 1 (coding exon 1) of the ZNHIT2 gene. This alteration results from a G to A substitution at nucleotide position 1168, causing the valine (V) at amino acid position 390 to be replaced by a methionine (M). 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