rs1554777807

Variant names:

• chr10-210023-G-T
• rs1554777807
• NM_001370100.5:c.251G>T

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2 PM5 PP3

The NM_001370100.5(ZMYND11):​c.251G>T​(p.Gly84Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G84E) has been classified as Likely pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZMYND11 NM_001370100.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.80
• 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: Uncertain_significance. The variant received 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr10-210023-G-A is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 4278593.Status of the report is criteria_provided_single_submitter, 1 stars.
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.81

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.251G>T	p.Gly84Val	missense	Exon 3 of 15	NP_001357029.1	Q15326-1
	ZMYND11	NM_001370097.3		c.251G>T	p.Gly84Val	missense	Exon 3 of 15	NP_001357026.1	Q15326-1
	ZMYND11	NM_001370098.2		c.251G>T	p.Gly84Val	missense	Exon 3 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.251G>T	p.Gly84Val	missense	Exon 3 of 15	ENSP00000371017.6	Q15326-1
	ZMYND11	ENST00000397962.8	TSL:1	c.251G>T	p.Gly84Val	missense	Exon 3 of 15	ENSP00000381053.3	Q15326-1
	ZMYND11	ENST00000558098.4	TSL:1	c.251G>T	p.Gly84Val	missense	Exon 2 of 13	ENSP00000452959.1	Q15326-3

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
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.018	T
MetaRNN	Pathogenic	0.81	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	2.0	M
PhyloP100		9.8
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-7.3	D
REVEL	Uncertain	0.57
Sift	Uncertain	0.0030	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.80
MVP		0.85
MPC		3.1
ClinPred		0.99	D
GERP RS		5.6
Varity_R		0.70
gMVP		0.91
Mutation Taster		=156/144	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: rs1554777807; hg19: chr10-255963;