10-180016-G-A

Position:

• chr10-180016-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 in gene, where missense usually causes diseases (based on misZ statistic), ZMYND11. . Gene score misZ 3.7109 (greater than the threshold 3.09). Trascript score misZ 4.725 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, syndromic complex neurodevelopmental disorder, autosomal dominant non-syndromic intellectual disability, intellectual disability, autosomal dominant 30.
• 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	Protein	UniProt
ZMYND11	NM_001370100.5	c.4G>A	p.Ala2Thr	missense_variant	2/15	ENST00000381604.9	NP_001357029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMYND11	ENST00000381604.9	c.4G>A	p.Ala2Thr	missense_variant	2/15	5	NM_001370100.5	ENSP00000371017	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

- -

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
MutationAssessor	Benign	0.90	.;L;L;.;L;L;.;L;.;L;.;L
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;