8-56441346-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_001135690.3(PENK):c.730G>A(p.Asp244Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000992 in 1,613,712 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Consequence
NM_001135690.3 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 |
---|---|---|---|---|---|---|---|---|
PENK | NM_001135690.3 | c.730G>A | p.Asp244Asn | missense_variant | Exon 4 of 4 | ENST00000451791.7 | NP_001129162.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PENK | ENST00000451791.7 | c.730G>A | p.Asp244Asn | missense_variant | Exon 4 of 4 | 1 | NM_001135690.3 | ENSP00000400894.2 | ||
PENK | ENST00000314922.3 | c.730G>A | p.Asp244Asn | missense_variant | Exon 2 of 2 | 1 | ENSP00000324248.3 | |||
PENK | ENST00000517415.1 | c.130-4270G>A | intron_variant | Intron 1 of 1 | 3 | ENSP00000430268.1 | ||||
PENK | ENST00000523274.1 | n.*46G>A | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251126Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135736
GnomAD4 exome AF: 0.00000889 AC: 13AN: 1461542Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727082
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74338
ClinVar
Submissions by phenotype
not specified Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at