rs7901346

Variant names:

• chr10-240248-G-A
• rs7901346
• NM_001370100.5:c.753+137G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001370100.5(ZMYND11):​c.753+137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00236 in 706,690 control chromosomes in the GnomAD database, including 24 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 0.0082 (16 hom., cov: 33)
  • Exomes 𝑓: 0.00075 (8 hom.)
• Consequence: ZMYND11 NM_001370100.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 10 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, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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=-0.91).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0082 (1249/152290) while in subpopulation AFR AF = 0.0284 (1180/41540). AF 95% confidence interval is 0.0271. There are 16 homozygotes in GnomAd4. There are 568 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1249 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370100.5. 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
	ZMYND11	NM_001370100.5	MANE Select	c.753+137G>A		intron	N/A	NP_001357029.1	Q15326-1
	ZMYND11	NM_001370097.3		c.753+137G>A		intron	N/A	NP_001357026.1	Q15326-1
	ZMYND11	NM_001370098.2		c.753+137G>A		intron	N/A	NP_001357027.1	Q15326-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYND11	ENST00000381604.9	TSL:5 MANE Select	c.753+137G>A		intron	N/A	ENSP00000371017.6	Q15326-1
	ZMYND11	ENST00000397962.8	TSL:1	c.753+137G>A		intron	N/A	ENSP00000381053.3	Q15326-1
	ZMYND11	ENST00000558098.4	TSL:1	c.753+137G>A		intron	N/A	ENSP00000452959.1	Q15326-3

Frequencies

GnomAD3 genomes AF: 0.00820 AC: 1248 AN: 152172 Hom.: 17 Cov.: 33

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.000754 AC: 418 AN: 554400 Hom.: 8 AF XY: 0.000674 AC XY: 192 AN XY: 284834

African (AFR) AF: 0.0276 AC: 346 AN: 12556

American (AMR) AF: 0.000926 AC: 14 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12918

East Asian (EAS) AF: 0.00 AC: 0 AN: 25922

South Asian (SAS) AF: 0.00 AC: 0 AN: 36418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28198

Middle Eastern (MID) AF: 0.00245 AC: 5 AN: 2042

European-Non Finnish (NFE) AF: 0.0000228 AC: 9 AN: 393964

Other (OTH) AF: 0.00161 AC: 44 AN: 27266

GnomAD4 genome AF: 0.00820 AC: 1249 AN: 152290 Hom.: 16 Cov.: 33 AF XY: 0.00763 AC XY: 568 AN XY: 74470

African (AFR) AF: 0.0284 AC: 1180 AN: 41540

American (AMR) AF: 0.00320 AC: 49 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68032

Other (OTH) AF: 0.00805 AC: 17 AN: 2112

Alfa AF: 0.00835 Hom.: 3

Bravo AF: 0.00937

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.98
DANN	Benign	0.82
PhyloP100		-0.013
Mutation Taster		=100/0	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: rs7901346; hg19: chr10-286188;