Variant chr13-19851877-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001142684.2(ZMYM5):c.304T>C(p.Ser102Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000476 in 1,611,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00049 ( 0 hom. )

Consequence

ZMYM5
NM_001142684.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0680

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.039132506).

BP6

Variant 13-19851877-A-G is Benign according to our data. Variant chr13-19851877-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2459049.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMYM5	NM_001142684.2 link	c.304T>C	p.Ser102Pro	missense_variant	3/8	ENST00000337963.9	NP_001136156.1	Q9UJ78-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZMYM5	ENST00000337963.9 link	c.304T>C	p.Ser102Pro	missense_variant	3/8	5	NM_001142684.2	ENSP00000337034.4		Q9UJ78-4

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000309

AC:

AN:

248958

Hom.:

AF XY:

0.000275

AC XY:

AN XY:

134632

show subpopulations

Gnomad AFR exome

AF:

0.000124

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.000593

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000489

AC:

714

AN:

1459576

Hom.:

Cov.:

AF XY:

0.000446

AC XY:

324

AN XY:

726060

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000226

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000300

Gnomad4 NFE exome

AF:

0.000611

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

AF:

0.000348

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.000268

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000659

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000660

Hom.:

Bravo

AF:

0.000344

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000313

AC:

EpiCase

AF:

0.000927

EpiControl

AF:

0.000533

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.62

CADD

Benign

1.8

DANN

Benign

0.83

DEOGEN2

Benign

0.0023

T;T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.58

T;.;T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.039

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.65

N;.;N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.4

N;N;D;N

REVEL

Benign

0.057

Sift

Benign

0.29

T;T;T;T

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.0020

B;.;B;B

Vest4

0.059

MVP

0.014

MPC

0.019

ClinPred

0.039

GERP RS

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.047

gMVP

0.060

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