Variant rs1135401797 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2PP2PP5_Very_Strong

The NM_001370100.5(ZMYND11):c.76C>T(p.Arg26Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,460,928 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZMYND11
NM_001370100.5 missense

Scores

Clinical Significance

Pathogenic/Likely pathogenic criteria provided, multiple submitters, no conflicts P:2

Conservation

PhyloP100: 4.76

Variant links:

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]

ZMYND11 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 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 10-180088-C-T is Pathogenic according to our data. Variant chr10-180088-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 431123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYND11	NM_001370100.5 linkuse as main transcript	c.76C>T	p.Arg26Trp	missense_variant	2/15	ENST00000381604.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYND11	ENST00000381604.9 linkuse as main transcript	c.76C>T	p.Arg26Trp	missense_variant	2/15	5	NM_001370100.5	P4	Q15326-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1460928

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726784

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 30

Pathogenic:1

Pathogenic, criteria provided, single submitter

clinical testing

Groupe Hospitalier Pitie Salpetriere, UF Genomique du Developpement, Assistance Publique Hopitaux de Paris

Jan 06, 2017

Intellectual disability; dysmorphism (hypertelorism ) -

not provided

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

GeneDx

May 24, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34216016, 28708303) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.18

T;T;.;T;.;T;.;.;T;.;.;.

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.93

LIST_S2

Pathogenic

0.98

D;.;D;D;D;D;D;D;D;.;D;D

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.69

D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.38

MutationAssessor

Benign

1.8

.;L;L;.;L;L;.;L;.;L;.;L

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-5.2

D;D;D;.;D;D;D;.;D;.;D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.0020

D;D;D;.;D;D;D;.;D;.;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D;D;D;D;D;D;D

Polyphen

1.0, 0.99

.;.;.;D;.;.;.;.;D;.;.;.

Vest4

0.92, 0.79, 0.79, 0.79, 0.89, 0.79, 0.80, 0.77, 0.77

MutPred

0.39

Gain of ubiquitination at K29 (P = 0.0505);Gain of ubiquitination at K29 (P = 0.0505);Gain of ubiquitination at K29 (P = 0.0505);Gain of ubiquitination at K29 (P = 0.0505);Gain of ubiquitination at K29 (P = 0.0505);Gain of ubiquitination at K29 (P = 0.0505);Gain of ubiquitination at K29 (P = 0.0505);Gain of ubiquitination at K29 (P = 0.0505);Gain of ubiquitination at K29 (P = 0.0505);Gain of ubiquitination at K29 (P = 0.0505);Gain of ubiquitination at K29 (P = 0.0505);Gain of ubiquitination at K29 (P = 0.0505);

MVP

0.77

MPC

2.4

ClinPred

0.99

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.98

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over