NM_001370100.5:c.1688dupG

Variant names:

• chr10-252348-T-TG
• rs1554795149
• NM_001370100.5:c.1688dupG

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001370100.5(ZMYND11):​c.1688dupG​(p.Cys563TrpfsTer5) variant causes a frameshift, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZMYND11 NM_001370100.5 frameshift, splice_region
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.67
• Publications: 0 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: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 10 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

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.1688dupG	p.Cys563TrpfsTer5	frameshift splice_region	Exon 15 of 15	NP_001357029.1	Q15326-1
	ZMYND11	NM_001370097.3		c.1688dupG	p.Cys563TrpfsTer5	frameshift splice_region	Exon 15 of 15	NP_001357026.1	Q15326-1
	ZMYND11	NM_001370098.2		c.1688dupG	p.Cys563TrpfsTer5	frameshift splice_region	Exon 15 of 15	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.1688dupG	p.Cys563TrpfsTer5	frameshift splice_region	Exon 15 of 15	ENSP00000371017.6	Q15326-1
	ZMYND11	ENST00000397962.8	TSL:1	c.1688dupG	p.Cys563TrpfsTer5	frameshift splice_region	Exon 15 of 15	ENSP00000381053.3	Q15326-1
	ZMYND11	ENST00000381584.6	TSL:1	n.*1630dupG		splice_region non_coding_transcript_exon	Exon 16 of 16	ENSP00000370996.2	J3QKD2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.7

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: rs1554795149; hg19: chr10-298288;