chr10-248575-G-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBS1_SupportingBS2

The NM_001370100.5(ZMYND11):c.1467G>T(p.Glu489Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000459 in 1,612,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

ZMYND11
NM_001370100.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

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:

LOC107984190 (HGNC:):

LOC107984190 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PP2

Missense variant in the ZMYND11 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 14 curated pathogenic missense variants (we use a threshold of 10). The gene has 21 curated benign missense variants. Gene score misZ: 3.7109 (above the threshold of 3.09). Trascript score misZ: 4.725 (above the threshold of 3.09). GenCC associations: The gene is linked to intellectual disability, autosomal dominant 40, syndromic complex neurodevelopmental disorder, autosomal dominant non-syndromic intellectual disability, intellectual disability, autosomal dominant 30.

BP4

Computational evidence support a benign effect (MetaRNN=0.21112907).

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.00005 (73/1460010) while in subpopulation NFE AF= 0.0000639 (71/1111656). AF 95% confidence interval is 0.0000516. There are 0 homozygotes in gnomad4_exome. There are 36 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAdExome4 at 73 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYND11	NM_001370100.5 link	c.1467G>T	p.Glu489Asp	missense_variant	Exon 13 of 15	ENST00000381604.9	NP_001357029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYND11	ENST00000381604.9 link	c.1467G>T	p.Glu489Asp	missense_variant	Exon 13 of 15	5	NM_001370100.5	ENSP00000371017.6		Q15326-1A0A0A0MRY2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0000242

AC:

AN:

248414

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

134402

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000532

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000500

AC:

AN:

1460010

Hom.:

Cov.:

AF XY:

0.0000496

AC XY:

AN XY:

726236

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:

0.00

Gnomad4 NFE exome

AF:

0.0000639

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

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

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 03, 2017

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.046

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

Eigen

Benign

-0.0047

Eigen_PC

Benign

-0.071

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.87

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

M_CAP

Benign

0.0043

MetaRNN

Benign

0.21

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.90

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

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.1

N;N;N;.;N;N;N;.;N;.;N;N;.

REVEL

Benign

0.19

Sift

Benign

0.079

T;D;T;.;D;T;D;.;T;.;T;D;.

Sift4G

Benign

0.13

T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

1.0, 0.98, 1.0

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

Vest4

0.42

MVP

0.31

MPC

1.0

ClinPred

0.18

GERP RS

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.62

gMVP

0.56

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