Genetic Variant ZMYM5:p.Ala372Thr (chr13-19835614-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001142684.2(ZMYM5):c.1114G>A(p.Ala372Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000257 in 1,367,646 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

ZMYM5
NM_001142684.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022583216).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYM5	NM_001142684.2 link	c.1114G>A	p.Ala372Thr	missense_variant	Exon 7 of 8	ENST00000337963.9	NP_001136156.1	Q9UJ78-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZMYM5	ENST00000337963.9 link	c.1114G>A	p.Ala372Thr	missense_variant	Exon 7 of 8	5	NM_001142684.2	ENSP00000337034.4	Q9UJ78-4
ZMYM5	ENST00000382909.5 link	n.970G>A		non_coding_transcript_exon_variant	Exon 4 of 5	1
ZMYM5	ENST00000535942.5 link	n.1309G>A		non_coding_transcript_exon_variant	Exon 5 of 6	5

Frequencies

GnomAD3 genomes

AF:

0.000473

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00269

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000450

AC:

112

AN:

248744

Hom.:

AF XY:

0.000555

AC XY:

AN XY:

135164

show subpopulations

Gnomad AFR exome

AF:

0.0000648

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.0000996

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000311

Gnomad OTH exome

AF:

0.000827

GnomAD4 exome

AF:

0.000230

AC:

280

AN:

1215398

Hom.:

Cov.:

AF XY:

0.000312

AC XY:

188

AN XY:

602336

show subpopulations

Gnomad4 AFR exome

AF:

0.0000760

Gnomad4 AMR exome

AF:

0.000965

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000108

Gnomad4 OTH exome

AF:

0.000477

GnomAD4 genome

AF:

0.000473

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000385

Hom.:

Bravo

AF:

0.000521

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000419

AC:

ExAC

AF:

0.000389

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000356

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 16, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1114G>A (p.A372T) alteration is located in exon 7 (coding exon 5) of the ZMYM5 gene. This alteration results from a G to A substitution at nucleotide position 1114, causing the alanine (A) at amino acid position 372 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0082

T;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.098

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

D;.

M_CAP

Benign

0.0086

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.035

Sift

Benign

0.26

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.016

B;.

Vest4

0.26

MVP

0.030

ClinPred

0.033

GERP RS

3.0

Varity_R

0.052

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over