NM_001281775.3:c.3115G>A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_001281775.3(ZMYND8):​c.3115G>A​(p.Val1039Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZMYND8
NM_001281775.3 missense

Scores

6
8
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.85
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1
In a binding_site (size 0) in uniprot entity ZMYD8_HUMAN
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ZMYND8NM_001281775.3 linkc.3115G>A p.Val1039Met 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
ZMYND8ENST00000471951.7 linkc.3115G>A p.Val1039Met missense_variant Exon 19 of 23 1 NM_001281775.3 ENSP00000420095.2 Q9ULU4-7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251372
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135856
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:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461884
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727242
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 24, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2977G>A (p.V993M) alteration is located in exon 19 (coding exon 19) of the ZMYND8 gene. This alteration results from a G to A substitution at nucleotide position 2977, causing the valine (V) at amino acid position 993 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.72
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.040
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.48
T;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Eigen
Pathogenic
0.87
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.99
D;D;D;.;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.66
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Benign
1.8
L;.;.;L;L;L;.;.;.;.;.;.;.;.;.
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-2.3
N;N;N;.;N;N;.;.;N;.;.;N;N;N;.
REVEL
Benign
0.25
Sift
Uncertain
0.0050
D;D;D;.;D;D;.;.;D;.;.;D;D;D;.
Sift4G
Benign
0.087
T;T;D;T;T;T;D;D;D;D;T;D;T;D;T
Polyphen
1.0
D;.;D;.;.;.;.;.;.;D;D;D;.;D;.
Vest4
0.80
MutPred
0.25
Gain of helix (P = 0.0225);.;.;Gain of helix (P = 0.0225);Gain of helix (P = 0.0225);Gain of helix (P = 0.0225);.;.;.;.;.;.;.;.;.;
MVP
0.52
MPC
1.2
ClinPred
0.86
D
GERP RS
5.5
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
3.0
Varity_R
0.67
gMVP
0.71

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.

Other links and lift over

dbSNP: rs778818570; hg19: chr20-45853111; API