rs140678079

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_201599.3(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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T1269T) has been classified as Likely benign.

Frequency

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

Exomes 𝑓: 0.000062 ( 0 hom. 29 hem. )

Consequence

ZMYM3
NM_201599.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0790

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

intellectual developmental disorder, X-linked 112
Inheritance: XL Classification: MODERATE Submitted by: G2P
intellectual disability
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics
syndromic intellectual disability
Inheritance: XL Classification: NO_KNOWN Submitted by: Illumina

ZMYM3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

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

BS2

High Hemizygotes in GnomAd4 at 3 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_201599.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZMYM3	NM_201599.3	MANE Select	c.3806C>T	p.Thr1269Met	missense	Exon 24 of 25	NP_963893.1	Q14202-1
ZMYM3	NM_005096.3		c.3806C>T	p.Thr1269Met	missense	Exon 24 of 25	NP_005087.1	Q14202-1
ZMYM3	NM_001171162.1		c.3770C>T	p.Thr1257Met	missense	Exon 24 of 25	NP_001164633.1	Q14202-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZMYM3	ENST00000314425.9	TSL:1 MANE Select	c.3806C>T	p.Thr1269Met	missense	Exon 24 of 25	ENSP00000322845.5	Q14202-1
ZMYM3	ENST00000373998.5	TSL:1	c.3770C>T	p.Thr1257Met	missense	Exon 24 of 25	ENSP00000363110.1	Q14202-2
ZMYM3	ENST00000373988.5	TSL:5	c.3812C>T	p.Thr1271Met	missense	Exon 24 of 25	ENSP00000363100.1	A6NHB5

Frequencies

GnomAD3 genomes

AF:

0.000144

AC:

AN:

110894

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.0000672

AC:

AN:

148808

AF XY:

0.0000496

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 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

African (AFR)

AF:

0.000387

AC:

AN:

25863

American (AMR)

AF:

0.0000311

AC:

AN:

32194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18498

East Asian (EAS)

AF:

0.0000672

AC:

AN:

29776

South Asian (SAS)

AF:

0.0000198

AC:

AN:

50381

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39478

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4042

European-Non Finnish (NFE)

AF:

0.0000581

AC:

AN:

826732

Other (OTH)

AF:

0.0000888

AC:

AN:

45028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000144

AC:

AN:

110947

Hom.:

Cov.:

AF XY:

0.0000905

AC XY:

AN XY:

33161

show subpopulations

African (AFR)

AF:

0.000459

AC:

AN:

30493

American (AMR)

AF:

0.00

AC:

AN:

10408

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.000282

AC:

AN:

3541

South Asian (SAS)

AF:

0.00

AC:

AN:

2561

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5933

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

52956

Other (OTH)

AF:

0.00

AC:

AN:

1507

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000934

Hom.:

Bravo

AF:

0.000162

ESP6500AA

AF:

0.000782

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000913

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.0

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.063

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.62

M_CAP

Benign

0.016

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

PhyloP100

0.079

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.60

REVEL

Benign

0.069

Sift

Benign

0.11

Sift4G

Benign

0.10

Polyphen

1.0

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

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over