X-77968990-C-T
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001029891.3(PGAM4):c.649G>A(p.Val217Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,209,686 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001029891.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PGAM4 | NM_001029891.3 | c.649G>A | p.Val217Ile | missense_variant | 1/1 | ENST00000458128.3 | NP_001025062.1 | |
ATP7A | NM_000052.7 | c.-21-2631C>T | intron_variant | ENST00000341514.11 | NP_000043.4 | |||
ATP7A | NM_001282224.2 | c.-21-2631C>T | intron_variant | NP_001269153.1 | ||||
ATP7A | NR_104109.2 | n.144-2631C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PGAM4 | ENST00000458128.3 | c.649G>A | p.Val217Ile | missense_variant | 1/1 | NM_001029891.3 | ENSP00000412189 | P1 | ||
ATP7A | ENST00000341514.11 | c.-21-2631C>T | intron_variant | 1 | NM_000052.7 | ENSP00000345728 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000445 AC: 5AN: 112249Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34401
GnomAD3 exomes AF: 0.0000927 AC: 17AN: 183319Hom.: 0 AF XY: 0.0000442 AC XY: 3AN XY: 67811
GnomAD4 exome AF: 0.0000474 AC: 52AN: 1097382Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 9AN XY: 363226
GnomAD4 genome AF: 0.0000445 AC: 5AN: 112304Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 34466
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 27, 2022 | The c.649G>A (p.V217I) alteration is located in exon 1 (coding exon 1) of the PGAM4 gene. This alteration results from a G to A substitution at nucleotide position 649, causing the valine (V) at amino acid position 217 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Dec 05, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at