4-184117016-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_153343.4(ENPP6):c.695G>A(p.Arg232His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000039 in 1,614,166 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R232C) has been classified as Uncertain significance.
Frequency
Consequence
NM_153343.4 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 |
---|---|---|---|---|---|---|---|---|---|---|
ENPP6 | ENST00000296741.7 | c.695G>A | p.Arg232His | missense_variant | Exon 5 of 8 | 1 | NM_153343.4 | ENSP00000296741.2 | ||
ENPP6 | ENST00000512353.1 | c.431G>A | p.Arg144His | missense_variant | Exon 6 of 6 | 3 | ENSP00000423497.1 | |||
ENPP6 | ENST00000510054.1 | n.83G>A | non_coding_transcript_exon_variant | Exon 2 of 3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000197 AC: 30AN: 152172Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251434Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135894
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461876Hom.: 0 Cov.: 31 AF XY: 0.0000206 AC XY: 15AN XY: 727234
GnomAD4 genome AF: 0.000197 AC: 30AN: 152290Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15AN XY: 74462
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.695G>A (p.R232H) alteration is located in exon 5 (coding exon 5) of the ENPP6 gene. This alteration results from a G to A substitution at nucleotide position 695, causing the arginine (R) at amino acid position 232 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