20-47221364-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001281775.3(ZMYND8):c.3367G>A(p.Ala1123Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,614,182 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 0 hom. )

Consequence

ZMYND8
NM_001281775.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.108

Publications

1 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: G2P, Ambry Genetics
syndromic complex neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: ClinGen
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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018911302).

BP6

Variant 20-47221364-C-T is Benign according to our data. Variant chr20-47221364-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2408090.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 48 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281775.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZMYND8	NM_001281775.3	MANE Select	c.3367G>A	p.Ala1123Thr	missense	Exon 20 of 23	NP_001268704.1	Q9ULU4-7
ZMYND8	NM_001363714.1		c.3388G>A	p.Ala1130Thr	missense	Exon 20 of 23	NP_001350643.1	Q9ULU4-19
ZMYND8	NM_001281773.3		c.3307G>A	p.Ala1103Thr	missense	Exon 21 of 24	NP_001268702.1	Q9ULU4-11

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZMYND8	ENST00000471951.7	TSL:1 MANE Select	c.3367G>A	p.Ala1123Thr	missense	Exon 20 of 23	ENSP00000420095.2	Q9ULU4-7
ZMYND8	ENST00000446994.6	TSL:1	c.3307G>A	p.Ala1103Thr	missense	Exon 20 of 23	ENSP00000396725.3	Q9ULU4-11
ZMYND8	ENST00000461685.5	TSL:1	c.3229G>A	p.Ala1077Thr	missense	Exon 20 of 23	ENSP00000418210.1	Q9ULU4-13

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.000191

AC:

AN:

251442

AF XY:

0.000162

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000781

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.000977

GnomAD4 exome

AF:

0.000228

AC:

333

AN:

1461870

Hom.:

Cov.:

AF XY:

0.000232

AC XY:

169

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.000850

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000223

AC:

248

AN:

1112006

Other (OTH)

AF:

0.000513

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000315

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0000722

AC:

AN:

41576

American (AMR)

AF:

0.00157

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68024

Other (OTH)

AF:

0.00189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000202

Hom.:

Bravo

AF:

0.000559

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000189

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.68

DEOGEN2

Benign

0.010

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.23

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0097

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.11

PrimateAI

Benign

0.28

PROVEAN

Benign

0.010

REVEL

Benign

0.023

Sift

Benign

0.44

Sift4G

Benign

0.74

Polyphen

0.0020

Vest4

0.18

MVP

0.38

MPC

0.38

ClinPred

0.0075

GERP RS

0.013

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.018

gMVP

0.16

Mutation Taster

=83/17

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over