chr20-47236423-C-T

Position:

• chr20-47236423-C-T

Variant summary

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

The NM_001281775.3(ZMYND8):​c.2759G>A​(p.Gly920Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZMYND8 NM_001281775.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.52

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ZMYND8. . Gene score misZ 4.0385 (greater than the threshold 3.09). Trascript score misZ 5.0127 (greater than threshold 3.09). GenCC has associacion of gene with autism spectrum disorder.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYND8	NM_001281775.3	c.2759G>A	p.Gly920Glu	missense_variant	16/23	ENST00000471951.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYND8	ENST00000471951.7	c.2759G>A	p.Gly920Glu	missense_variant	16/23	1	NM_001281775.3	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

GeneDx

Feb 03, 2023

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.92	D;D;D;.;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.55	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.64	D
MutationAssessor	Benign	0.90	L;.;.;L;L;L;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D;D;D;N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.0	N;N;N;.;N;N;.;N;N;.;.;N;N;N;.
REVEL	Uncertain	0.39
Sift	Uncertain	0.0040	D;D;D;.;D;D;.;D;T;.;.;D;D;D;.
Sift4G	Benign	0.69	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.74	P;.;D;.;.;.;.;.;.;D;B;D;.;D;.
Vest4		0.71
MutPred		0.14		Loss of sheet (P = 0.0357);.;.;Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);Loss of sheet (P = 0.0357);.;.;.;.;.;.;.;.;.;
MVP		0.62
MPC		1.3
ClinPred		0.76	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-45865167;