20-47225746-T-C

Variant names:

• chr20-47225746-T-C
• rs3091566
• NM_001281775.3:c.3017-1190A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001281775.3(ZMYND8):​c.3017-1190A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 151,402 control chromosomes in the GnomAD database, including 8,851 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (8851 hom., cov: 28)
• Consequence: ZMYND8 NM_001281775.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.668
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.556 is higher than 0.05.

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.3017-1190A>G		intron	N/A	NP_001268704.1	Q9ULU4-7
	ZMYND8	NM_001363714.1		c.3038-1190A>G		intron	N/A	NP_001350643.1	Q9ULU4-19
	ZMYND8	NM_001281773.3		c.2957-1190A>G		intron	N/A	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.3017-1190A>G		intron	N/A	ENSP00000420095.2	Q9ULU4-7
	ZMYND8	ENST00000446994.6	TSL:1	c.2957-1190A>G		intron	N/A	ENSP00000396725.3	Q9ULU4-11
	ZMYND8	ENST00000461685.5	TSL:1	c.2879-1190A>G		intron	N/A	ENSP00000418210.1	Q9ULU4-13

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44360 AN: 151286 Hom.: 8832 Cov.: 28

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.176

Gnomad OTH AF: 0.266

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.293 AC: 44431 AN: 151402 Hom.: 8851 Cov.: 28 AF XY: 0.293 AC XY: 21657 AN XY: 73994

African (AFR) AF: 0.562 AC: 23113 AN: 41156

American (AMR) AF: 0.231 AC: 3504 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 910 AN: 3462

East Asian (EAS) AF: 0.110 AC: 567 AN: 5154

South Asian (SAS) AF: 0.387 AC: 1853 AN: 4794

European-Finnish (FIN) AF: 0.178 AC: 1863 AN: 10470

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.176 AC: 11934 AN: 67878

Other (OTH) AF: 0.266 AC: 558 AN: 2094

Alfa AF: 0.243 Hom.: 2170

Bravo AF: 0.308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.57
PhyloP100		-0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3091566; hg19: chr20-45854487;