10-209908-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2 PP2 BP4_Moderate BP6_Moderate

The NM_001370100.5(ZMYND11):c.136G>A(p.Gly46Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G46D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ZMYND11 NM_001370100.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.82

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 Likely_benign. Variant got -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant where missense usually causes diseases, ZMYND11
• BP4: Computational evidence support a benign effect (MetaRNN=0.23690239).
• BP6: Variant 10-209908-G-A is Benign according to our data. Variant chr10-209908-G-A is described in ClinVar as [Benign]. Clinvar id is 2806539.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYND11	NM_001370100.5	c.136G>A	p.Gly46Ser	missense_variant	3/15	ENST00000381604.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYND11	ENST00000381604.9	c.136G>A	p.Gly46Ser	missense_variant	3/15	5	NM_001370100.5	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251274 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135780

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461526 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 727058

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.0094	T
BayesDel_noAF	Benign	-0.25
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.069	T;T;T;.;T;.;T;.;.;T;.;.;.;.;.
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.93	D;.;D;D;D;D;D;D;D;D;.;D;.;D;D
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.24	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.66	T
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-2.9	D;N;N;N;.;N;N;N;.;N;.;N;N;N;.
REVEL	Benign	0.096
Sift	Benign	0.083	T;D;D;D;.;D;D;D;.;D;.;T;D;D;.
Sift4G	Benign	0.17	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.041, 0.28	.;.;.;.;B;.;.;.;.;B;.;.;.;.;.
Vest4		0.31, 0.30, 0.33, 0.33, 0.29, 0.32, 0.32, 0.33, 0.33, 0.32, 0.33
MutPred		0.46		Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);.;Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);Gain of disorder (P = 0.0527);.;Gain of disorder (P = 0.0527);.;
MVP		0.068
MPC		1.5
ClinPred		0.79	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs1396699311; hg19: chr10-255848; COSMIC: COSV59077808;