Variant X-71241084-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_201599.3(ZMYM3):c.3945C>T(p.Asn1315Asn) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.08

Variant links:

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]

ZMYM3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 109 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMYM3	NM_201599.3 link	c.3945C>T	p.Asn1315Asn	synonymous_variant	25/25	ENST00000314425.9	NP_963893.1	Q14202-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMYM3	ENST00000314425.9 link	c.3945C>T	p.Asn1315Asn	synonymous_variant	25/25	1	NM_201599.3	ENSP00000322845.5		Q14202-1

Frequencies

GnomAD3 genomes

AF:

0.00343

AC:

380

AN:

110692

Hom.:

Cov.:

AF XY:

0.00331

AC XY:

109

AN XY:

32908

show subpopulations

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.:

AF XY:

0.00400

AC XY:

256

AN XY:

64073

show subpopulations

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.:

Cov.:

AF XY:

0.00449

AC XY:

1627

AN XY:

362036

show subpopulations

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.:

Cov.:

AF XY:

0.00331

AC XY:

109

AN XY:

32972

show subpopulations

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.:

Bravo

AF:

0.00275

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over