rs1135401797

chr10-180088-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP2 PP5_Moderate

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 Pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZMYND11 NM_001370100.5 missense
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 4.76

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 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ZMYND11
• PP5: Variant 10-180088-C-T is Pathogenic according to our data. Variant chr10-180088-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 431123.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYND11	NM_001370100.5	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	c.76C>T	p.Arg26Trp	missense_variant	2/15	5	NM_001370100.5	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460928 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726784

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.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

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 ) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.35
Cadd	Pathogenic	27
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	D
LIST_S2	Pathogenic	0.98	D;.;D;D;D;D;D;D;D;.;D;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.69	D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.38	T
PrimateAI	Pathogenic	0.87	D
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	D
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

Other links and lift over

dbSNP: rs1135401797; hg19: chr10-226028; COSMIC: COSV59081419;