10-3138239-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_014889.4(PITRM1):c.3016G>C(p.Asp1006His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,612,076 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 (★★).
Frequency
Consequence
NM_014889.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PITRM1 | NM_014889.4 | c.3016G>C | p.Asp1006His | missense_variant | 26/27 | ENST00000224949.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PITRM1 | ENST00000224949.9 | c.3016G>C | p.Asp1006His | missense_variant | 26/27 | 1 | NM_014889.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152222Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000883 AC: 22AN: 249114Hom.: 0 AF XY: 0.0000962 AC XY: 13AN XY: 135164
GnomAD4 exome AF: 0.000111 AC: 162AN: 1459854Hom.: 0 Cov.: 31 AF XY: 0.000112 AC XY: 81AN XY: 726394
GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152222Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74360
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 12, 2021 | The c.3019G>C (p.D1007H) alteration is located in exon 26 (coding exon 26) of the PITRM1 gene. This alteration results from a G to C substitution at nucleotide position 3019, causing the aspartic acid (D) at amino acid position 1007 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 908 of the PITRM1 protein (p.Asp908His). This variant is present in population databases (rs758352717, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PITRM1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1435139). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at