22-35400476-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006739.4(MCM5):āc.38A>Gā(p.Asp13Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. D13D) has been classified as Likely benign.
Frequency
Consequence
NM_006739.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MCM5 | NM_006739.4 | c.38A>G | p.Asp13Gly | missense_variant | 2/17 | ENST00000216122.9 | |
MCM5 | XM_006724242.5 | c.38A>G | p.Asp13Gly | missense_variant | 2/18 | ||
MCM5 | XM_047441366.1 | c.38A>G | p.Asp13Gly | missense_variant | 2/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MCM5 | ENST00000216122.9 | c.38A>G | p.Asp13Gly | missense_variant | 2/17 | 1 | NM_006739.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152218Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251062Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135836
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461750Hom.: 0 Cov.: 31 AF XY: 0.0000220 AC XY: 16AN XY: 727188
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152218Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74378
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 12, 2023 | The c.38A>G (p.D13G) alteration is located in exon 2 (coding exon 1) of the MCM5 gene. This alteration results from a A to G substitution at nucleotide position 38, causing the aspartic acid (D) at amino acid position 13 to be replaced by a glycine (G). 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 | Jul 08, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with MCM5-related conditions. This variant is present in population databases (rs141005002, ExAC 0.003%). This sequence change replaces aspartic acid with glycine at codon 13 of the MCM5 protein (p.Asp13Gly). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and glycine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at