20-47227277-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001281775.3(ZMYND8):​c.2942G>T​(p.Arg981Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R981C) has been classified as Uncertain significance.

Frequency

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

Consequence

ZMYND8
NM_001281775.3 missense

Scores

4
10
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11
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 2 ACMG points.

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.2942G>T p.Arg981Leu missense_variant Exon 18 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.2942G>T p.Arg981Leu missense_variant Exon 18 of 23 1 NM_001281775.3 ENSP00000420095.2 Q9ULU4-7

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251442
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135892
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
AF:
0.00000137
AC:
2
AN:
1461788
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727214
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Oct 16, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2804G>T (p.R935L) alteration is located in exon 18 (coding exon 18) of the ZMYND8 gene. This alteration results from a G to T substitution at nucleotide position 2804, causing the arginine (R) at amino acid position 935 to be replaced by a leucine (L). 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
0.99
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.13
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Benign
0.065
T;.;.;.;.;.;.;.;.;.;.;.;.;.;.
Eigen
Uncertain
0.64
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Pathogenic
0.98
D;D;D;.;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.040
D
MetaRNN
Uncertain
0.57
D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.087
D
MutationAssessor
Benign
1.3
L;.;.;L;L;L;.;.;.;.;.;.;.;.;.
PrimateAI
Pathogenic
0.89
D
PROVEAN
Uncertain
-2.5
D;D;D;.;D;D;.;.;D;.;.;D;D;D;.
REVEL
Uncertain
0.31
Sift
Benign
0.064
T;T;T;.;T;T;.;.;T;.;.;T;T;T;.
Sift4G
Uncertain
0.040
D;D;T;D;D;D;T;T;T;T;D;T;D;T;T
Polyphen
1.0
D;.;D;.;.;.;.;.;.;D;D;D;.;D;.
Vest4
0.71
MutPred
0.52
Loss of MoRF binding (P = 0.019);.;.;Loss of MoRF binding (P = 0.019);Loss of MoRF binding (P = 0.019);Loss of MoRF binding (P = 0.019);.;.;.;.;.;.;.;.;.;
MVP
0.71
MPC
1.3
ClinPred
0.68
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.55
gMVP
0.65

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: rs781522203; hg19: chr20-45856020; API