Variant X-71241341-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000314425.9(ZMYM3):c.3806C>T(p.Thr1269Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000693 in 1,182,939 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 32 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000062 ( 0 hom. 29 hem. )

Consequence

ZMYM3
ENST00000314425.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0790

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016864955).

BS2

High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMYM3	NM_201599.3 linkuse as main transcript	c.3806C>T	p.Thr1269Met	missense_variant	24/25	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.3806C>T	p.Thr1269Met	missense_variant	24/25	1	NM_201599.3	ENSP00000322845	P4	Q14202-1

Frequencies

GnomAD3 genomes

AF:

0.000144

AC:

AN:

110894

Hom.:

Cov.:

AF XY:

0.0000906

AC XY:

AN XY:

33098

show subpopulations

Gnomad AFR

AF:

0.000460

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000282

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000189

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000672

AC:

AN:

148808

Hom.:

AF XY:

0.0000496

AC XY:

AN XY:

40338

show subpopulations

Gnomad AFR exome

AF:

0.000266

Gnomad AMR exome

AF:

0.0000852

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000247

Gnomad SAS exome

AF:

0.0000712

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000156

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000616

AC:

AN:

1071992

Hom.:

Cov.:

AF XY:

0.0000850

AC XY:

AN XY:

341052

show subpopulations

Gnomad4 AFR exome

AF:

0.000387

Gnomad4 AMR exome

AF:

0.0000311

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000672

Gnomad4 SAS exome

AF:

0.0000198

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000581

Gnomad4 OTH exome

AF:

0.0000888

GnomAD4 genome

AF:

0.000144

AC:

AN:

110947

Hom.:

Cov.:

AF XY:

0.0000905

AC XY:

AN XY:

33161

show subpopulations

Gnomad4 AFR

AF:

0.000459

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000282

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000189

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000582

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000913

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 20, 2024

The c.3806C>T (p.T1269M) alteration is located in exon 24 (coding exon 23) of the ZMYM3 gene. This alteration results from a C to T substitution at nucleotide position 3806, causing the threonine (T) at amino acid position 1269 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.0

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

T;.;T;T

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.62

T;T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.016

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.;.;.

MutationTaster

Benign

0.94

D;D;D;D;D

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.60

N;N;N;N

REVEL

Benign

0.069

Sift

Benign

0.11

T;T;D;T

Sift4G

Benign

0.10

T;T;D;T

Polyphen

1.0

D;D;.;.

Vest4

0.093

MVP

0.093

ClinPred

0.016

GERP RS

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.028

gMVP

0.63

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