X-71241084-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_201599.3(ZMYM3):c.3945C>T(p.Asn1315=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00457 in 1,207,394 control chromosomes in the GnomAD database, including 14 homozygotes. There are 1,736 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (1 hom., 109 hem., cov: 21)
  • Exomes 𝑓: 0.0047 (13 hom. 1627 hem.)
• Consequence: ZMYM3 NM_201599.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.08

Genes affected

ZMYM3 (HGNC:13054): (zinc finger MYM-type containing 3) This gene is located on the X chromosome and is subject to X inactivation. It is highly conserved in vertebrates and most abundantly expressed in the brain. The encoded protein is a component of histone deacetylase-containing multiprotein complexes that function through modifying chromatin structure to keep genes silent. A chromosomal translocation (X;13) involving this gene is associated with X-linked cognitive disability. Several alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant X-71241084-G-A is Benign according to our data. Variant chrX-71241084-G-A is described in ClinVar as [Benign]. Clinvar id is 782794.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-71241084-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.08 with no splicing effect.
• BS2: High Hemizygotes in GnomAd at 109 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYM3	NM_201599.3	c.3945C>T	p.Asn1315=	synonymous_variant	25/25	ENST00000314425.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYM3	ENST00000314425.9	c.3945C>T	p.Asn1315=	synonymous_variant	25/25	1	NM_201599.3	P4

Frequencies

GnomAD3 genomes AF: 0.00343 AC: 380 AN: 110692 Hom.: 1 Cov.: 21 AF XY: 0.00331 AC XY: 109 AN XY: 32908

Gnomad AFR AF: 0.000427

Gnomad AMI AF: 0.00735

Gnomad AMR AF: 0.000870

Gnomad ASJ AF: 0.00800

Gnomad EAS AF: 0.00256

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00880

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00507

Gnomad OTH AF: 0.00201

GnomAD3 exomes AF: 0.00415 AC: 744 AN: 179331 Hom.: 1 AF XY: 0.00400 AC XY: 256 AN XY: 64073

Gnomad AFR exome AF: 0.000466

Gnomad AMR exome AF: 0.00232

Gnomad ASJ exome AF: 0.00961

Gnomad EAS exome AF: 0.00109

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0105

Gnomad NFE exome AF: 0.00509

Gnomad OTH exome AF: 0.00426

GnomAD4 exome AF: 0.00468 AC: 5137 AN: 1096648 Hom.: 13 Cov.: 31 AF XY: 0.00449 AC XY: 1627 AN XY: 362036

Gnomad4 AFR exome AF: 0.000341

Gnomad4 AMR exome AF: 0.00217

Gnomad4 ASJ exome AF: 0.00817

Gnomad4 EAS exome AF: 0.00683

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0113

Gnomad4 NFE exome AF: 0.00483

Gnomad4 OTH exome AF: 0.00371

GnomAD4 genome AF: 0.00343 AC: 380 AN: 110746 Hom.: 1 Cov.: 21 AF XY: 0.00331 AC XY: 109 AN XY: 32972

Gnomad4 AFR AF: 0.000427

Gnomad4 AMR AF: 0.000869

Gnomad4 ASJ AF: 0.00800

Gnomad4 EAS AF: 0.00257

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00880

Gnomad4 NFE AF: 0.00507

Gnomad4 OTH AF: 0.00198

Alfa AF: 0.00505 Hom.: 59

Bravo AF: 0.00275

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

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.23
Dann	Benign	0.72

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: rs2272778; hg19: chrX-70460934;