10-180049-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4BS1_Supporting
The NM_001370100.5(ZMYND11):c.37A>G(p.Lys13Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
ZMYND11
NM_001370100.5 missense
NM_001370100.5 missense
Scores
2
6
9
Clinical Significance
Conservation
PhyloP100: 8.79
Genes affected
ZMYND11 (HGNC:16966): (zinc finger MYND-type containing 11) The protein encoded by this gene was first identified by its ability to bind the adenovirus E1A protein. The protein localizes to the nucleus. It functions as a transcriptional repressor, and expression of E1A inhibits this repression. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, ZMYND11
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2937649).
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0000205 (30/1461522) while in subpopulation NFE AF= 0.0000261 (29/1111788). AF 95% confidence interval is 0.0000183. There are 0 homozygotes in gnomad4_exome. There are 13 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ZMYND11 | NM_001370100.5 | c.37A>G | p.Lys13Glu | missense_variant | 2/15 | ENST00000381604.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ZMYND11 | ENST00000381604.9 | c.37A>G | p.Lys13Glu | missense_variant | 2/15 | 5 | NM_001370100.5 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248716Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135152
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GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461522Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13AN XY: 727058
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GnomAD4 genome ? Cov.: 33
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Cov.:
33
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0
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Intellectual disability, autosomal dominant 30 Uncertain:1
Uncertain significance, criteria provided, single submitter | research | UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill | Jan 01, 2020 | ZMYND11 c.37A>G (p.Lys13Glu) is a missense variant that changes a single amino acid from a lysine to a glutamic acid. This variant has been rarely observed in human population databases (< 1 in 20,000 alleles). It has not been reported previously in the clinical literature and is of uncertain clinical significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2022 | 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. ClinVar contains an entry for this variant (Variation ID: 1064553). This variant has not been reported in the literature in individuals affected with ZMYND11-related conditions. This variant is present in population databases (rs759490914, gnomAD 0.0009%). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 13 of the ZMYND11 protein (p.Lys13Glu). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T;.;T;.;T;.;.;T;.;.;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D;D;D;D;D;D;.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;.;N;N;N;.;N;.;N;N
REVEL
Benign
Sift
Benign
T;T;T;.;T;T;T;.;T;.;T;T
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.0060
.;.;.;B;.;.;.;.;B;.;.;.
Vest4
0.56, 0.65, 0.66, 0.66, 0.56, 0.65, 0.66, 0.64, 0.64, 0.69
MutPred
Loss of MoRF binding (P = 0.0052);Loss of MoRF binding (P = 0.0052);Loss of MoRF binding (P = 0.0052);Loss of MoRF binding (P = 0.0052);Loss of MoRF binding (P = 0.0052);Loss of MoRF binding (P = 0.0052);Loss of MoRF binding (P = 0.0052);Loss of MoRF binding (P = 0.0052);Loss of MoRF binding (P = 0.0052);Loss of MoRF binding (P = 0.0052);Loss of MoRF binding (P = 0.0052);Loss of MoRF binding (P = 0.0052);
MVP
MPC
2.1
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at