rs149688628
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_012082.4(ZFPM2):āc.3294G>Cā(p.Glu1098Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_012082.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFPM2 | NM_012082.4 | c.3294G>C | p.Glu1098Asp | missense_variant | 8/8 | ENST00000407775.7 | |
ZFPM2-AS1 | NR_125797.1 | n.191-4934C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFPM2 | ENST00000407775.7 | c.3294G>C | p.Glu1098Asp | missense_variant | 8/8 | 1 | NM_012082.4 | P1 | |
ZFPM2-AS1 | ENST00000520433.5 | n.212-4934C>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152204Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 247896Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134430
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461038Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 726722
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152322Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74476
ClinVar
Submissions by phenotype
46,XY sex reversal 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 25, 2019 | In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The aspartic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. This variant is present in population databases (rs149688628, ExAC 0.01%) but has not been reported in the literature in individuals with a ZFPM2-related disease. This sequence change replaces glutamic acid with aspartic acid at codon 1098 of the ZFPM2 protein (p.Glu1098Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at