rs757483496

Variant names:

• chr20-47236391-C-A
• rs757483496
• NM_001281775.3:c.2791G>T

Your query was ambiguous. Multiple possible variants found:

• chr20-47236391-C-A
• chr20-47236391-C-G
• chr20-47236391-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001281775.3(ZMYND8):​c.2791G>T​(p.Ala931Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. 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. A931T) has been classified 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: 1.76
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics
• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: ClinGen
• autism spectrum disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.081464946).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001281775.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYND8	NM_001281775.3	MANE Select	c.2791G>T	p.Ala931Ser	missense	Exon 16 of 23	NP_001268704.1	Q9ULU4-7
	ZMYND8	NM_001363714.1		c.2812G>T	p.Ala938Ser	missense	Exon 16 of 23	NP_001350643.1	Q9ULU4-19
	ZMYND8	NM_001281773.3		c.2731G>T	p.Ala911Ser	missense	Exon 17 of 24	NP_001268702.1	Q9ULU4-11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYND8	ENST00000471951.7	TSL:1 MANE Select	c.2791G>T	p.Ala931Ser	missense	Exon 16 of 23	ENSP00000420095.2	Q9ULU4-7
	ZMYND8	ENST00000446994.6	TSL:1	c.2731G>T	p.Ala911Ser	missense	Exon 16 of 23	ENSP00000396725.3	Q9ULU4-11
	ZMYND8	ENST00000461685.5	TSL:1	c.2653G>T	p.Ala885Ser	missense	Exon 16 of 23	ENSP00000418210.1	Q9ULU4-13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	ZMYND8-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.53	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.8
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.18
Sift	Benign	0.17	T
Sift4G	Benign	1.0	T
Polyphen		0.17	B
Vest4		0.083
MutPred		0.10		Gain of phosphorylation at A911 (P = 0.042)
MVP		0.33
MPC		0.58
ClinPred		0.14	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.29
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs757483496; hg19: chr20-45865135;