10-180032-G-C

Position:

• chr10-180032-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP2

The NM_001370100.5(ZMYND11):​c.20G>C​(p.Arg7Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZMYND11 NM_001370100.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.32

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), ZMYND11. . Gene score misZ 3.7109 (greater than the threshold 3.09). Trascript score misZ 4.725 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, syndromic complex neurodevelopmental disorder, autosomal dominant non-syndromic intellectual disability, intellectual disability, autosomal dominant 30.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMYND11	NM_001370100.5	c.20G>C	p.Arg7Thr	missense_variant	2/15	ENST00000381604.9	NP_001357029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMYND11	ENST00000381604.9	c.20G>C	p.Arg7Thr	missense_variant	2/15	5	NM_001370100.5	ENSP00000371017	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.20G>C (p.R7T) alteration is located in exon 1 (coding exon 1) of the ZMYND11 gene. This alteration results from a G to C substitution at nucleotide position 20, causing the arginine (R) at amino acid position 7 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.089	D
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	26
DANN	Benign	0.97
DEOGEN2	Benign	0.089	T;T;.;T;.;T;.;.;T;.;.;.
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Pathogenic	0.97	D;.;D;D;D;D;D;D;D;.;D;D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.46	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.8	.;L;L;.;L;L;.;L;.;L;.;L
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.0	D;N;N;.;N;N;N;.;N;.;N;N
REVEL	Benign	0.27
Sift	Uncertain	0.0020	D;D;D;.;D;D;D;.;D;.;D;D
Sift4G	Uncertain	0.018	D;D;D;D;T;D;D;D;D;D;D;D
Polyphen		0.80	.;.;.;P;.;.;.;.;P;.;.;.
Vest4		0.46, 0.62, 0.59, 0.56, 0.50, 0.60, 0.61, 0.61, 0.58
MutPred		0.32		Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);Gain of sheet (P = 0.0266);
MVP		0.23
MPC		2.2
ClinPred		0.97	D
GERP RS		6.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.94

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-225972;