chr20-47249374-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001281775.3(ZMYND8):c.1687G>C(p.Val563Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,614,132 control chromosomes in the GnomAD database, including 181 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0082 ( 5 hom., cov: 32)

Exomes 𝑓: 0.012 ( 176 hom. )

Consequence

ZMYND8
NM_001281775.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.27

Publications

8 publications found

Variant links:

Genes affected

ZMYND8 (HGNC:9397): (zinc finger MYND-type containing 8) The protein encoded by this gene is a receptor for activated C-kinase (RACK) protein. The encoded protein has been shown to bind in vitro to activated protein kinase C beta I. In addition, this protein is a cutaneous T-cell lymphoma-associated antigen. Finally, the protein contains a bromodomain and two zinc fingers, and is thought to be a transcriptional regulator. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ZMYND8 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P
autism spectrum disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ZMYND8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047740936).

BP6

Variant 20-47249374-C-G is Benign according to our data. Variant chr20-47249374-C-G is described in ClinVar as Benign. ClinVar VariationId is 777918.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.0121 (17715/1461880) while in subpopulation MID AF = 0.0347 (200/5768). AF 95% confidence interval is 0.0307. There are 176 homozygotes in GnomAdExome4. There are 8585 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1241 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYND8	NM_001281775.3 link	c.1687G>C	p.Val563Leu	missense_variant	Exon 13 of 23	ENST00000471951.7	NP_001268704.1	Q9ULU4-7A6H8Y8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYND8	ENST00000471951.7 link	c.1687G>C	p.Val563Leu	missense_variant	Exon 13 of 23	1	NM_001281775.3	ENSP00000420095.2		Q9ULU4-7

Frequencies

GnomAD3 genomes

AF:

0.00816

AC:

1242

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.0429

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0125

Gnomad OTH

AF:

0.0144

GnomAD2 exomes

AF:

0.00880

AC:

2212

AN:

251482

AF XY:

0.00867

show subpopulations

Gnomad AFR exome

AF:

0.00234

Gnomad AMR exome

AF:

0.00543

Gnomad ASJ exome

AF:

0.0473

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00222

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.0134

GnomAD4 exome

AF:

0.0121

AC:

17715

AN:

1461880

Hom.:

176

Cov.:

AF XY:

0.0118

AC XY:

8585

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00314

AC:

105

AN:

33480

American (AMR)

AF:

0.00575

AC:

257

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0466

AC:

1217

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00247

AC:

213

AN:

86256

European-Finnish (FIN)

AF:

0.00298

AC:

159

AN:

53420

Middle Eastern (MID)

AF:

0.0347

AC:

200

AN:

5768

European-Non Finnish (NFE)

AF:

0.0131

AC:

14541

AN:

1112006

Other (OTH)

AF:

0.0169

AC:

1023

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

978

1955

2933

3910

4888

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

584

1168

1752

2336

2920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00815

AC:

1241

AN:

152252

Hom.:

Cov.:

AF XY:

0.00760

AC XY:

566

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

41572

American (AMR)

AF:

0.00484

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0429

AC:

149

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5176

South Asian (SAS)

AF:

0.00145

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00170

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0124

AC:

846

AN:

68004

Other (OTH)

AF:

0.0142

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

132

197

263

329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0143

Hom.:

Bravo

AF:

0.00872

TwinsUK

AF:

0.0129

AC:

ALSPAC

AF:

0.0125

AC:

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0133

AC:

114

ExAC

AF:

0.00848

AC:

1030

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.0141

EpiControl

AF:

0.0137

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.021

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

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.86

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

MetaRNN

Benign

0.0048

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

MetaSVM

Uncertain

-0.16

MutationAssessor

Benign

0.81

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

PhyloP100

3.3

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.2

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

REVEL

Uncertain

0.32

Sift

Uncertain

0.0040

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

Sift4G

Benign

0.27

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

Polyphen

0.078

B;.;B;.;.;.;.;.;.;.;B;B;B;.;B;.

Vest4

0.19

MVP

0.75

MPC

0.39

ClinPred

0.029

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.20

gMVP

0.12

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over