10-209909-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_001370100.5(ZMYND11):c.137G>A(p.Gly46Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,950 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G46S) has been classified as Benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: ZMYND11 NM_001370100.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.91

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ZMYND11

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYND11	NM_001370100.5	c.137G>A	p.Gly46Asp	missense_variant	3/15	ENST00000381604.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYND11	ENST00000381604.9	c.137G>A	p.Gly46Asp	missense_variant	3/15	5	NM_001370100.5	P4

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151950 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151950 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74196

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

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

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

ZMYND11: PM2:Supporting, BP1 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.079	T;T;T;.;T;.;T;.;.;T;.;.;.;.;.
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;.;D;D;D;D;D;D;D;D;.;D;.;D;D
M_CAP	Benign	0.0027	T
MetaRNN	Uncertain	0.57	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-0.70	T
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.6	D;D;N;N;.;D;D;N;.;D;.;D;N;D;.
REVEL	Benign	0.27
Sift	Uncertain	0.018	D;D;D;T;.;D;D;D;.;D;.;D;D;D;.
Sift4G	Benign	0.20	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.36, 0.84	.;.;.;.;B;.;.;.;.;P;.;.;.;.;.
Vest4		0.50, 0.42, 0.46, 0.45, 0.44, 0.47, 0.46, 0.45, 0.46, 0.45, 0.46
MutPred		0.50		Gain of ubiquitination at K50 (P = 0.0551);Gain of ubiquitination at K50 (P = 0.0551);.;Gain of ubiquitination at K50 (P = 0.0551);Gain of ubiquitination at K50 (P = 0.0551);Gain of ubiquitination at K50 (P = 0.0551);Gain of ubiquitination at K50 (P = 0.0551);Gain of ubiquitination at K50 (P = 0.0551);Gain of ubiquitination at K50 (P = 0.0551);Gain of ubiquitination at K50 (P = 0.0551);Gain of ubiquitination at K50 (P = 0.0551);Gain of ubiquitination at K50 (P = 0.0551);.;Gain of ubiquitination at K50 (P = 0.0551);.;
MVP		0.16
MPC		2.8
ClinPred		0.99	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.60
gMVP		0.91

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: rs1274061878; hg19: chr10-255849;