Genetic Variant NM_005095.3:c.545G>A (chr1-35359384-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

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

The NM_005095.3(ZMYM4):c.545G>A(p.Arg182Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,594,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

ZMYM4
NM_005095.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.61

Publications

0 publications found

Variant links:

Genes affected

ZMYM4 (HGNC:13055): (zinc finger MYM-type containing 4) Predicted to enable DNA binding activity. Involved in cytoskeleton organization and regulation of cell morphogenesis. [provided by Alliance of Genome Resources, Apr 2022]

ZMYM4 links:

ZMYM4-AS1 (HGNC:40624): (ZMYM4 antisense RNA 1)

ZMYM4-AS1 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=0.03280416).

BS2

High AC in GnomAd4 at 12 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005095.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZMYM4	NM_005095.3	MANE Select	c.545G>A	p.Arg182Gln	missense	Exon 3 of 30	NP_005086.2
ZMYM4	NM_001375653.1		c.554G>A	p.Arg185Gln	missense	Exon 3 of 30	NP_001362582.1
ZMYM4	NM_001350138.2		c.449G>A	p.Arg150Gln	missense	Exon 4 of 31	NP_001337067.1	Q5VZL5-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZMYM4	ENST00000314607.11	TSL:2 MANE Select	c.545G>A	p.Arg182Gln	missense	Exon 3 of 30	ENSP00000322915.6	Q5VZL5-1
ZMYM4	ENST00000933225.1		c.545G>A	p.Arg182Gln	missense	Exon 3 of 30	ENSP00000603284.1
ZMYM4	ENST00000933226.1		c.545G>A	p.Arg182Gln	missense	Exon 3 of 30	ENSP00000603285.1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000221

AC:

AN:

226566

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000266

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000555

AC:

AN:

1442742

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

717012

show subpopulations

African (AFR)

AF:

0.0000934

AC:

AN:

32106

American (AMR)

AF:

0.00

AC:

AN:

39310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25128

East Asian (EAS)

AF:

0.00

AC:

AN:

39560

South Asian (SAS)

AF:

0.0000123

AC:

AN:

81284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53014

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1107124

Other (OTH)

AF:

0.0000336

AC:

AN:

59564

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152002

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.000265

AC:

AN:

41434

American (AMR)

AF:

0.00

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67930

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000132

Hom.:

Bravo

AF:

0.0000945

ESP6500AA

AF:

0.000685

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.034

Eigen

Benign

-0.56

Eigen_PC

Benign

-0.39

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.82

M_CAP

Benign

0.0060

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

1.6

PrimateAI

Benign

0.40

PROVEAN

Benign

0.12

REVEL

Benign

0.022

Sift

Benign

0.10

Sift4G

Benign

0.51

Polyphen

0.024

Vest4

0.33

MVP

0.043

MPC

0.099

ClinPred

0.059

GERP RS

2.6

Varity_R

0.032

gMVP

0.38

Mutation Taster

=92/8

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