Variant X-71241348-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000314425.9(ZMYM3):c.3803-4A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00095 in 1,173,233 control chromosomes in the GnomAD database, including 6 homozygotes. There are 263 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0052 ( 2 hom., 121 hem., cov: 22)

Exomes 𝑓: 0.00051 ( 4 hom. 142 hem. )

Consequence

ZMYM3
ENST00000314425.9 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00002394

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -2.21

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant X-71241348-T-C is Benign according to our data. Variant chrX-71241348-T-C is described in ClinVar as [Benign]. Clinvar id is 711143.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00519 (575/110825) while in subpopulation AFR AF= 0.0183 (556/30417). AF 95% confidence interval is 0.017. There are 2 homozygotes in gnomad4. There are 121 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMYM3	NM_201599.3 linkuse as main transcript	c.3803-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000314425.9	NP_963893.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMYM3	ENST00000314425.9 linkuse as main transcript	c.3803-4A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_201599.3	ENSP00000322845	P4	Q14202-1

Frequencies

GnomAD3 genomes

AF:

0.00519

AC:

575

AN:

110771

Hom.:

Cov.:

AF XY:

0.00367

AC XY:

121

AN XY:

32973

show subpopulations

Gnomad AFR

AF:

0.0183

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00154

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.00134

GnomAD3 exomes

AF:

0.00162

AC:

228

AN:

141168

Hom.:

AF XY:

0.00115

AC XY:

AN XY:

35794

show subpopulations

Gnomad AFR exome

AF:

0.0201

Gnomad AMR exome

AF:

0.000268

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:

0.0000165

Gnomad OTH exome

AF:

0.000555

GnomAD4 exome

AF:

0.000507

AC:

539

AN:

1062408

Hom.:

Cov.:

AF XY:

0.000425

AC XY:

142

AN XY:

333834

show subpopulations

Gnomad4 AFR exome

AF:

0.0182

Gnomad4 AMR exome

AF:

0.000449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000404

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000134

Gnomad4 OTH exome

AF:

0.000986

GnomAD4 genome

AF:

0.00519

AC:

575

AN:

110825

Hom.:

Cov.:

AF XY:

0.00366

AC XY:

121

AN XY:

33037

show subpopulations

Gnomad4 AFR

AF:

0.0183

Gnomad4 AMR

AF:

0.00154

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00132

Alfa

AF:

0.00261

Hom.:

Bravo

AF:

0.00575

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ZMYM3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.030

DANN

Benign

0.51

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000024

dbscSNV1_RF

Benign

0.0040

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