10-246791-C-G

Variant names:

• chr10-246791-C-G
• rs672601340
• NM_001370100.5:c.976C>G
• ZMYND11 p.Gln326Glu

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001370100.5(ZMYND11):​c.976C>G​(p.Gln326Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,844 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q326Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ZMYND11 NM_001370100.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.82
• 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: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC107984190 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 7 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.976C>G	p.Gln326Glu	missense	Exon 11 of 15	NP_001357029.1	Q15326-1
	ZMYND11	NM_001370097.3		c.976C>G	p.Gln326Glu	missense	Exon 11 of 15	NP_001357026.1	Q15326-1
	ZMYND11	NM_001370098.2		c.976C>G	p.Gln326Glu	missense	Exon 11 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.976C>G	p.Gln326Glu	missense	Exon 11 of 15	ENSP00000371017.6	Q15326-1
	ZMYND11	ENST00000397962.8	TSL:1	c.976C>G	p.Gln326Glu	missense	Exon 11 of 15	ENSP00000381053.3	Q15326-1
	ZMYND11	ENST00000558098.4	TSL:1	c.976C>G	p.Gln326Glu	missense	Exon 10 of 13	ENSP00000452959.1	Q15326-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461844 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.057	T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.85	L
PhyloP100		7.8
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.30
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.056	T
Varity_R		0.75
gMVP		0.82
Mutation Taster		=32/68	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs672601340;

hg19: chr10-292731;

COSMIC: COSV59082689;