10-209902-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP2 BP4

The NM_001370100.5(ZMYND11):c.130G>A(p.Val44Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: ZMYND11 NM_001370100.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.11

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ZMYND11
• BP4: Computational evidence support a benign effect (MetaRNN=0.3752646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYND11	NM_001370100.5	c.130G>A	p.Val44Ile	missense_variant	3/15	ENST00000381604.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYND11	ENST00000381604.9	c.130G>A	p.Val44Ile	missense_variant	3/15	5	NM_001370100.5	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Nov 08, 2019

Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
Cadd	Pathogenic	28
Dann	Uncertain	1.0
DEOGEN2	Benign	0.023	T;T;T;.;T;.;T;.;.;T;.;.;.;.;.
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;.;D;D;D;D;D;D;D;D;.;D;.;D;D
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.38	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.73	T
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.89	N;N;N;N;.;N;N;N;.;N;.;N;N;N;.
REVEL	Benign	0.24
Sift	Uncertain	0.011	D;T;T;T;.;T;T;T;.;T;.;D;T;T;.
Sift4G	Benign	0.34	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.98, 0.99	.;.;.;.;D;.;.;.;.;D;.;.;.;.;.
Vest4		0.25, 0.30, 0.31, 0.32, 0.29, 0.32, 0.31, 0.32, 0.28, 0.32
MutPred		0.22		Gain of methylation at K39 (P = 0.1057);Gain of methylation at K39 (P = 0.1057);.;Gain of methylation at K39 (P = 0.1057);Gain of methylation at K39 (P = 0.1057);Gain of methylation at K39 (P = 0.1057);Gain of methylation at K39 (P = 0.1057);Gain of methylation at K39 (P = 0.1057);Gain of methylation at K39 (P = 0.1057);Gain of methylation at K39 (P = 0.1057);Gain of methylation at K39 (P = 0.1057);Gain of methylation at K39 (P = 0.1057);.;Gain of methylation at K39 (P = 0.1057);.;
MVP		0.14
MPC		2.5
ClinPred		0.94	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-255842;