Genetic Variant ZMYM6:p.Glu1233Lys (chr1-34987385-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_007167.4(ZMYM6):c.3697G>A(p.Glu1233Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 1,613,918 control chromosomes in the GnomAD database, including 1,460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.056 ( 710 hom., cov: 33)

Exomes 𝑓: 0.0093 ( 750 hom. )

Consequence

ZMYM6
NM_007167.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.987

Publications

10 publications found

Variant links:

Genes affected

ZMYM6 (HGNC:13050): (zinc finger MYM-type containing 6) Predicted to enable DNA binding activity. Involved in cytoskeleton organization and regulation of cell morphogenesis. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZMYM6 Gene-Disease associations (from GenCC):

intellectual disability
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, G2P

ZMYM6 links:

ENSG00000271741 (HGNC:):

ENSG00000271741 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014627576).

BP6

Variant 1-34987385-C-T is Benign according to our data. Variant chr1-34987385-C-T is described in ClinVar as Benign. ClinVar VariationId is 3056816.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007167.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZMYM6	NM_007167.4	MANE Select	c.3697G>A	p.Glu1233Lys	missense	Exon 16 of 16	NP_009098.3	O95789-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZMYM6	ENST00000357182.9	TSL:1 MANE Select	c.3697G>A	p.Glu1233Lys	missense	Exon 16 of 16	ENSP00000349708.4	O95789-3
ZMYM6	ENST00000493328.5	TSL:1	n.5021G>A		non_coding_transcript_exon	Exon 15 of 15
ENSG00000271741	ENST00000487874.1	TSL:5	n.2147-3438G>A		intron	N/A	ENSP00000421752.1

Frequencies

GnomAD3 genomes

AF:

0.0562

AC:

8553

AN:

152148

Hom.:

707

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0246

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00411

Gnomad OTH

AF:

0.0378

GnomAD2 exomes

AF:

0.0182

AC:

4539

AN:

249210

AF XY:

0.0155

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.0126

Gnomad ASJ exome

AF:

0.0252

Gnomad EAS exome

AF:

0.00211

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00356

Gnomad OTH exome

AF:

0.0142

GnomAD4 exome

AF:

0.00927

AC:

13550

AN:

1461652

Hom.:

750

Cov.:

AF XY:

0.00881

AC XY:

6407

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.191

AC:

6381

AN:

33458

American (AMR)

AF:

0.0141

AC:

632

AN:

44692

Ashkenazi Jewish (ASJ)

AF:

0.0255

AC:

667

AN:

26130

East Asian (EAS)

AF:

0.00181

AC:

AN:

39678

South Asian (SAS)

AF:

0.0117

AC:

1007

AN:

86202

European-Finnish (FIN)

AF:

0.000150

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.0277

AC:

160

AN:

5766

European-Non Finnish (NFE)

AF:

0.00312

AC:

3474

AN:

1111934

Other (OTH)

AF:

0.0190

AC:

1149

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

684

1367

2051

2734

3418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

276

552

828

1104

1380

<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:

0.0564

AC:

8584

AN:

152266

Hom.:

710

Cov.:

AF XY:

0.0547

AC XY:

4070

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.185

AC:

7701

AN:

41524

American (AMR)

AF:

0.0246

AC:

376

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0233

AC:

AN:

3472

East Asian (EAS)

AF:

0.00174

AC:

AN:

5186

South Asian (SAS)

AF:

0.0102

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00412

AC:

280

AN:

68040

Other (OTH)

AF:

0.0374

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

356

712

1067

1423

1779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0285

Hom.:

738

Bravo

AF:

0.0636

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.170

AC:

617

ESP6500EA

AF:

0.00392

AC:

ExAC

AF:

0.0207

AC:

2503

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.00387

EpiControl

AF:

0.00528

ClinVar

ClinVar submissions

Significance:Benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

ZMYM6-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.056

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

PhyloP100

0.99

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.2

REVEL

Benign

0.097

Sift

Uncertain

0.014

Sift4G

Pathogenic

0.0

Polyphen

0.70

Vest4

0.16

MPC

0.85

ClinPred

0.035

GERP RS

5.1

Varity_R

0.23

gMVP

0.69

Mutation Taster

=79/21

polymorphism (auto)

(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

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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