X-71242172-C-T

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.3800G>A(p.Arg1267Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000772 in 1,178,976 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 27 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict 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 Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000080 ( 0 hom. 26 hem. )

Consequence

ZMYM3
NM_201599.3 missense, splice_region

Scores

Splicing: ADA: 0.004933

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.47

Publications

2 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=0.015719354).

BS2

High Hemizygotes in GnomAdExome4 at 26 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.3800G>A	p.Arg1267Gln	missense splice_region	Exon 23 of 25	NP_963893.1	Q14202-1
ZMYM3	NM_005096.3		c.3800G>A	p.Arg1267Gln	missense splice_region	Exon 23 of 25	NP_005087.1	Q14202-1
ZMYM3	NM_001171162.1		c.3764G>A	p.Arg1255Gln	missense splice_region	Exon 23 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.3800G>A	p.Arg1267Gln	missense splice_region	Exon 23 of 25	ENSP00000322845.5	Q14202-1
ZMYM3	ENST00000373998.5	TSL:1	c.3764G>A	p.Arg1255Gln	missense splice_region	Exon 23 of 25	ENSP00000363110.1	Q14202-2
ZMYM3	ENST00000373988.5	TSL:5	c.3806G>A	p.Arg1269Gln	missense splice_region	Exon 23 of 25	ENSP00000363100.1	A6NHB5

Frequencies

GnomAD3 genomes

AF:

0.0000533

AC:

AN:

112505

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000187

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:

0.0000751

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000457

AC:

AN:

131218

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000810

Gnomad NFE exome

AF:

0.0000930

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000797

AC:

AN:

1066471

Hom.:

Cov.:

AF XY:

0.0000748

AC XY:

AN XY:

347481

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25539

American (AMR)

AF:

0.0000336

AC:

AN:

29738

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18755

East Asian (EAS)

AF:

0.00

AC:

AN:

28255

South Asian (SAS)

AF:

0.00

AC:

AN:

50789

European-Finnish (FIN)

AF:

0.0000518

AC:

AN:

38578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3728

European-Non Finnish (NFE)

AF:

0.0000932

AC:

AN:

826200

Other (OTH)

AF:

0.000111

AC:

AN:

44889

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

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:

0.0000533

AC:

AN:

112505

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34647

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30974

American (AMR)

AF:

0.000187

AC:

AN:

10676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3579

South Asian (SAS)

AF:

0.00

AC:

AN:

2731

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6210

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.0000751

AC:

AN:

53242

Other (OTH)

AF:

0.00

AC:

AN:

1521

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000432

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000513

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Intellectual disability (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.61

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.060

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.019

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.1

PhyloP100

3.5

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.0

REVEL

Benign

0.041

Sift

Benign

0.28

Sift4G

Benign

0.60

Polyphen

0.20

Vest4

0.30

MutPred

0.26

Loss of MoRF binding (P = 0.0423)

MVP

0.38

ClinPred

0.16

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.79

Mutation Taster

=91/9

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0049

dbscSNV1_RF

Benign

0.036

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