10-180016-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 5P and 1B. PM2 PP2 PP5_Moderate BP4

The NM_001370100.5(ZMYND11):c.4G>A(p.Ala2Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZMYND11 NM_001370100.5 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 6.97

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ZMYND11
• PP5: Variant 10-180016-G-A is Pathogenic according to our data. Variant chr10-180016-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2442370.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.28828698).. Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYND11	NM_001370100.5	c.4G>A	p.Ala2Thr	missense_variant	2/15	ENST00000381604.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYND11	ENST00000381604.9	c.4G>A	p.Ala2Thr	missense_variant	2/15	5	NM_001370100.5	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, autosomal dominant 30 Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Laboratoire de Génétique Moléculaire, CHU Bordeaux

Mar 25, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	0.0041	T
BayesDel_noAF	Benign	-0.23
Cadd	Benign	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.012	T;T;.;T;.;T;.;.;T;.;.;.
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.97	D;.;D;D;D;D;D;D;D;.;D;D
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.29	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.59	N;N;N;.;N;N;N;.;N;.;N;N
REVEL	Benign	0.20
Sift	Uncertain	0.024	D;D;T;.;D;D;D;.;D;.;D;D
Sift4G	Benign	0.30	T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0, 0.0060	.;.;.;B;.;.;.;.;B;.;.;.
Vest4		0.31, 0.31, 0.33, 0.28, 0.33, 0.32, 0.32, 0.32, 0.30, 0.37
MutPred		0.23		Gain of glycosylation at A2 (P = 0.0153);Gain of glycosylation at A2 (P = 0.0153);Gain of glycosylation at A2 (P = 0.0153);Gain of glycosylation at A2 (P = 0.0153);Gain of glycosylation at A2 (P = 0.0153);Gain of glycosylation at A2 (P = 0.0153);Gain of glycosylation at A2 (P = 0.0153);Gain of glycosylation at A2 (P = 0.0153);Gain of glycosylation at A2 (P = 0.0153);Gain of glycosylation at A2 (P = 0.0153);Gain of glycosylation at A2 (P = 0.0153);Gain of glycosylation at A2 (P = 0.0153);
MVP		0.22
MPC		1.5
ClinPred		0.69	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.80

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: chr10-225956; COSMIC: COSV59079704;