dbSNP rs367618268: ZMYND8:p.Ala1025Ser (chr20-47224500-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001281775.3(ZMYND8):c.3073G>T(p.Ala1025Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1025T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

ZMYND8
NM_001281775.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.12

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2137276).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYND8	NM_001281775.3 link	c.3073G>T	p.Ala1025Ser	missense_variant	Exon 19 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.3073G>T	p.Ala1025Ser	missense_variant	Exon 19 of 23	1	NM_001281775.3	ENSP00000420095.2		Q9ULU4-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251198

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135766

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.070

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

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

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.97

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

M_CAP

Benign

0.027

MetaRNN

Benign

0.21

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

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.090

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

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.42

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

REVEL

Benign

0.15

Sift

Benign

0.26

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

Sift4G

Benign

0.25

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

Polyphen

0.12

B;.;B;.;.;.;.;.;.;P;P;P;.;B;.

Vest4

0.32

MutPred

0.29

Gain of phosphorylation at A1005 (P = 0.0124);.;.;Gain of phosphorylation at A1005 (P = 0.0124);Gain of phosphorylation at A1005 (P = 0.0124);Gain of phosphorylation at A1005 (P = 0.0124);.;.;.;.;.;.;.;.;.;

MVP

0.43

MPC

0.38

ClinPred

0.46

GERP RS

4.4

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.15

gMVP

0.54

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over