Genetic Variant ZMYM5:p.Arg348Leu (chr13-19835685-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001142684.2(ZMYM5):c.1043G>T(p.Arg348Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,214,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R348C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

ZMYM5
NM_001142684.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.14

Publications

2 publications found

Variant links:

Genes affected

ZMYM5 (HGNC:13029): (zinc finger MYM-type containing 5) Predicted to enable zinc ion binding activity. Involved in negative regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZMYM5 Gene-Disease associations (from GenCC):

multiple congenital anomalies/dysmorphic syndrome
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ZMYM5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23970947).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001142684.2. 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
	ZMYM5	NM_001142684.2	MANE Select	c.1043G>T	p.Arg348Leu	missense	Exon 7 of 8	NP_001136156.1	Q9UJ78-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZMYM5	ENST00000337963.9	TSL:5 MANE Select	c.1043G>T	p.Arg348Leu	missense	Exon 7 of 8	ENSP00000337034.4	Q9UJ78-4
ZMYM5	ENST00000382909.5	TSL:1	n.899G>T		non_coding_transcript_exon	Exon 4 of 5
ZMYM5	ENST00000854552.1		c.1043G>T	p.Arg348Leu	missense	Exon 6 of 7	ENSP00000524611.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000121

AC:

AN:

247434

AF XY:

0.0000149

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:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000165

AC:

AN:

1214476

Hom.:

Cov.:

AF XY:

0.00000166

AC XY:

AN XY:

601758

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26256

American (AMR)

AF:

0.00

AC:

AN:

37178

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16824

East Asian (EAS)

AF:

0.00

AC:

AN:

16794

South Asian (SAS)

AF:

0.0000121

AC:

AN:

82976

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4464

European-Non Finnish (NFE)

AF:

0.00000105

AC:

AN:

953458

Other (OTH)

AF:

0.00

AC:

AN:

43968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

Cov.:

ExAC

AF:

0.0000166

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.084

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.069

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.022

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

3.1

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.20

Sift

Benign

0.081

Sift4G

Pathogenic

0.0

Polyphen

0.0030

Vest4

0.55

MutPred

0.63

Gain of ubiquitination at K343 (P = 0.0453)

MVP

0.030

ClinPred

0.23

GERP RS

3.1

Varity_R

0.24

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over