20-47212721-G-T

Variant names:

• chr20-47212721-G-T
• NM_001281775.3:c.3489C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001281775.3(ZMYND8):​c.3489C>A​(p.Ser1163Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ZMYND8 NM_001281775.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.99

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2410236).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYND8	NM_001281775.3	c.3489C>A	p.Ser1163Arg	missense_variant	Exon 22 of 23	ENST00000471951.7	NP_001268704.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYND8	ENST00000471951.7	c.3489C>A	p.Ser1163Arg	missense_variant	Exon 22 of 23	1	NM_001281775.3	ENSP00000420095.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1458952 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725460

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3351C>A (p.S1117R) alteration is located in exon 22 (coding exon 22) of the ZMYND8 gene. This alteration results from a C to A substitution at nucleotide position 3351, causing the serine (S) at amino acid position 1117 to be replaced by an arginine (R). 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
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Uncertain	0.99
Eigen	Benign	0.041
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;.;D;D;D;D;D;D;D
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.24	T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.58	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.28	N;.;N;.;.;.;.;N;.
REVEL	Benign	0.22
Sift	Uncertain	0.014	D;.;D;.;.;.;.;D;.
Sift4G	Benign	0.12	T;T;T;D;D;D;T;D;T
Polyphen		0.0, 0.0010	.;.;.;.;.;B;B;B;.
Vest4		0.64
MutPred		0.21		.;.;.;.;.;.;Loss of ubiquitination at K1164 (P = 0.0193);.;.;
MVP		0.34
MPC		0.45
ClinPred		0.91	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.097

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: chr20-45841366;