chr16-14436763-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_002582.4(PARN):c.1874C>T(p.Ser625Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,591,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. S625S) has been classified as Likely benign.
Frequency
Consequence
NM_002582.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PARN | NM_002582.4 | c.1874C>T | p.Ser625Leu | missense_variant | 24/24 | ENST00000437198.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PARN | ENST00000437198.7 | c.1874C>T | p.Ser625Leu | missense_variant | 24/24 | 1 | NM_002582.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000473 AC: 72AN: 152134Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000200 AC: 42AN: 209510Hom.: 0 AF XY: 0.000178 AC XY: 20AN XY: 112488
GnomAD4 exome AF: 0.0000681 AC: 98AN: 1439114Hom.: 0 Cov.: 29 AF XY: 0.0000701 AC XY: 50AN XY: 713464
GnomAD4 genome ? AF: 0.000473 AC: 72AN: 152252Hom.: 0 Cov.: 32 AF XY: 0.000457 AC XY: 34AN XY: 74440
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 03, 2021 | DNA sequence analysis of the PARN gene demonstrated a sequence change, c.1874C>T, in exon 24 that results in an amino acid change, p.Ser625Leu. This sequence change has been described in gnomAD with a frequency of 0.19% in the African/African-American sub-population (dbSNP rs201963032). The p.Ser625Leu change affects a poorly conserved amino acid residue located in a domain of the PARN protein that is not known to be functional. The p.Ser625Leu substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change does not appear to have been previously described in patients with PARN-related disorders. Due to the lack of sufficient evidences, the clinical significance of the p.Ser625Leu change remains unknown at this time. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 15, 2023 | 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. - |
Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 4;C4225356:Dyskeratosis congenita, autosomal recessive 6 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at