10-222468-G-A

Variant names:

• chr10-222468-G-A
• rs2448384
• NM_001370100.5:c.438+1112G>A

Variant summary

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

The NM_001370100.5(ZMYND11):​c.438+1112G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 152,016 control chromosomes in the GnomAD database, including 31,846 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 0.65 (31846 hom., cov: 31)
• Consequence: ZMYND11 NM_001370100.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746
• Publications: 1 publications found

Genes affected

ZMYND11 (HGNC:16966): (zinc finger MYND-type containing 11) The protein encoded by this gene was first identified by its ability to bind the adenovirus E1A protein. The protein localizes to the nucleus. It functions as a transcriptional repressor, and expression of E1A inhibits this repression. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ZMYND11 Gene-Disease associations (from GenCC):

• syndromic complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• intellectual disability, autosomal dominant 30

  Inheritance: AD Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

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 (EAS) allele frequency at 95% confidence interval = 0.814 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYND11	NM_001370100.5	c.438+1112G>A		intron_variant	Intron 4 of 14	ENST00000381604.9	NP_001357029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYND11	ENST00000381604.9	c.438+1112G>A		intron_variant	Intron 4 of 14	5	NM_001370100.5	ENSP00000371017.6

Frequencies

GnomAD3 genomes AF: 0.645 AC: 98020 AN: 151898 Hom.: 31822 Cov.: 31

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.776

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.623

Gnomad OTH AF: 0.619

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

GnomAD4 genome AF: 0.645 AC: 98100 AN: 152016 Hom.: 31846 Cov.: 31 AF XY: 0.655 AC XY: 48677 AN XY: 74330

African (AFR) AF: 0.631 AC: 26171 AN: 41458

American (AMR) AF: 0.627 AC: 9573 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2054 AN: 3470

East Asian (EAS) AF: 0.835 AC: 4324 AN: 5180

South Asian (SAS) AF: 0.731 AC: 3523 AN: 4818

European-Finnish (FIN) AF: 0.776 AC: 8193 AN: 10560

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.623 AC: 42330 AN: 67956

Other (OTH) AF: 0.618 AC: 1300 AN: 2104

Alfa AF: 0.642 Hom.: 11282

Bravo AF: 0.636

Asia WGS AF: 0.758 AC: 2631 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.40
DANN	Benign	0.55
PhyloP100		-0.75
Mutation Taster		=100/0	polymorphism (auto)

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: rs2448384; hg19: chr10-268408;