10-206753-T-C

Variant names:

• chr10-206753-T-C
• rs2379078
• NM_001370100.5:c.117-3136T>C

Variant summary

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

The NM_001370100.5(ZMYND11):​c.117-3136T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,102 control chromosomes in the GnomAD database, including 6,932 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 (6932 hom., cov: 32)
• Consequence: ZMYND11 NM_001370100.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYND11	NM_001370100.5	c.117-3136T>C		intron_variant	Intron 2 of 14	ENST00000381604.9	NP_001357029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYND11	ENST00000381604.9	c.117-3136T>C		intron_variant	Intron 2 of 14	5	NM_001370100.5	ENSP00000371017.6

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44313 AN: 151984 Hom.: 6921 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.276

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

GnomAD4 genome AF: 0.291 AC: 44337 AN: 152102 Hom.: 6932 Cov.: 32 AF XY: 0.297 AC XY: 22067 AN XY: 74348

African (AFR) AF: 0.213 AC: 8862 AN: 41518

American (AMR) AF: 0.362 AC: 5538 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1091 AN: 3466

East Asian (EAS) AF: 0.485 AC: 2507 AN: 5172

South Asian (SAS) AF: 0.351 AC: 1692 AN: 4820

European-Finnish (FIN) AF: 0.361 AC: 3812 AN: 10552

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.294 AC: 20005 AN: 67980

Other (OTH) AF: 0.277 AC: 585 AN: 2110

Alfa AF: 0.297 Hom.: 23585

Bravo AF: 0.296

Asia WGS AF: 0.384 AC: 1330 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.6
DANN	Benign	0.28
PhyloP100		0.30
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: rs2379078; hg19: chr10-252693;