chr18-74635029-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_017757.3(ZNF407):āc.4010A>Gā(p.Tyr1337Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,613,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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_017757.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZNF407 | NM_017757.3 | c.4010A>G | p.Tyr1337Cys | missense_variant | 2/9 | ENST00000299687.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZNF407 | ENST00000299687.10 | c.4010A>G | p.Tyr1337Cys | missense_variant | 2/9 | 1 | NM_017757.3 | P2 | |
ZNF407 | ENST00000577538.5 | c.4010A>G | p.Tyr1337Cys | missense_variant | 1/7 | 2 | A2 | ||
ZNF407 | ENST00000309902.10 | c.4010A>G | p.Tyr1337Cys | missense_variant | 1/4 | 2 | |||
ZNF407 | ENST00000582337.5 | c.4010A>G | p.Tyr1337Cys | missense_variant | 2/5 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000184 AC: 28AN: 152208Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000723 AC: 18AN: 248886Hom.: 0 AF XY: 0.0000740 AC XY: 10AN XY: 135078
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461676Hom.: 0 Cov.: 41 AF XY: 0.0000234 AC XY: 17AN XY: 727122
GnomAD4 genome AF: 0.000184 AC: 28AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.000296 AC XY: 22AN XY: 74380
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 06, 2021 | The c.4010A>G (p.Y1337C) alteration is located in exon 1 (coding exon 1) of the ZNF407 gene. This alteration results from a A to G substitution at nucleotide position 4010, causing the tyrosine (Y) at amino acid position 1337 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 09, 2017 | - - |
ZNF407-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 28, 2023 | The ZNF407 c.4010A>G variant is predicted to result in the amino acid substitution p.Tyr1337Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.046% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/18-72346985-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 16, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at