Variant chrX-71240964-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_201599.3(ZMYM3):c.4065C>T(p.Arg1355Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,209,541 control chromosomes in the GnomAD database, including 3 homozygotes. There are 433 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., 24 hem., cov: 22)

Exomes 𝑓: 0.0013 ( 3 hom. 409 hem. )

Consequence

ZMYM3
NM_201599.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.962

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant X-71240964-G-A is Benign according to our data. Variant chrX-71240964-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 96662.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}. Variant chrX-71240964-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.962 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 24 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMYM3	NM_201599.3 link	c.4065C>T	p.Arg1355Arg	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.4065C>T	p.Arg1355Arg	synonymous_variant	25/25	1	NM_201599.3	ENSP00000322845.5		Q14202-1

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

112

AN:

111313

Hom.:

Cov.:

AF XY:

0.000716

AC XY:

AN XY:

33531

show subpopulations

Gnomad AFR

AF:

0.000163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00416

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0168

Gnomad NFE

AF:

0.00142

Gnomad OTH

AF:

0.00266

GnomAD3 exomes

AF:

0.000974

AC:

178

AN:

182730

Hom.:

AF XY:

0.000950

AC XY:

AN XY:

67354

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.000547

Gnomad ASJ exome

AF:

0.00255

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00161

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.00128

AC:

1409

AN:

1098176

Hom.:

Cov.:

AF XY:

0.00113

AC XY:

409

AN XY:

363534

show subpopulations

Gnomad4 AFR exome

AF:

0.0000757

Gnomad4 AMR exome

AF:

0.000597

Gnomad4 ASJ exome

AF:

0.00294

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000499

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.00142

Gnomad4 OTH exome

AF:

0.00165

GnomAD4 genome

AF:

0.000997

AC:

111

AN:

111365

Hom.:

Cov.:

AF XY:

0.000714

AC XY:

AN XY:

33593

show subpopulations

Gnomad4 AFR

AF:

0.000163

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00416

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00142

Gnomad4 OTH

AF:

0.00263

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.00116

EpiCase

AF:

0.00295

EpiControl

AF:

0.00219

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 20, 2013	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

1.9

DANN

Benign

0.73

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