chr6-29672639-G-C
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001109809.5(ZFP57):āc.1472C>Gā(p.Thr491Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,611,308 control chromosomes in the GnomAD database, including 13 homozygotes. 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).
Frequency
Consequence
NM_001109809.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZFP57 | NM_001109809.5 | c.1472C>G | p.Thr491Ser | missense_variant | 5/5 | ENST00000376883.2 | |
ZFP57 | NM_001366333.2 | c.1256C>G | p.Thr419Ser | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZFP57 | ENST00000376883.2 | c.1472C>G | p.Thr491Ser | missense_variant | 5/5 | 5 | NM_001109809.5 | P1 | |
ZFP57 | ENST00000488757.6 | c.1256C>G | p.Thr419Ser | missense_variant | 4/4 | 1 |
Frequencies
GnomAD3 genomes AF: 0.00216 AC: 328AN: 152136Hom.: 7 Cov.: 32
GnomAD3 exomes AF: 0.00153 AC: 375AN: 244546Hom.: 2 AF XY: 0.00158 AC XY: 212AN XY: 133844
GnomAD4 exome AF: 0.00126 AC: 1834AN: 1459054Hom.: 5 Cov.: 31 AF XY: 0.00127 AC XY: 924AN XY: 725444
GnomAD4 genome AF: 0.00220 AC: 335AN: 152254Hom.: 8 Cov.: 32 AF XY: 0.00242 AC XY: 180AN XY: 74424
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2023 | ZFP57: BP4, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 28, 2023 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 20, 2021 | The c.1472C>G (p.T491S) alteration is located in exon 4 (coding exon 4) of the ZFP57 gene. This alteration results from a C to G substitution at nucleotide position 1472, causing the threonine (T) at amino acid position 491 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Monogenic diabetes Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Personalized Diabetes Medicine Program, University of Maryland School of Medicine | Feb 01, 2019 | ACMG criteria: BP4 (Revel score 0.024 + 9 predictors)=VUS - |
Diabetes mellitus, transient neonatal, 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
ZFP57-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 19, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at