Variant chr1-35370383-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005095.3(ZMYM4):c.937A>G(p.Thr313Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000281 in 1,278,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 24)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

ZMYM4
NM_005095.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.68

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008849621).

BS2

High AC in GnomAd4 at 45 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYM4	NM_005095.3 linkuse as main transcript	c.937A>G	p.Thr313Ala	missense_variant	7/30	ENST00000314607.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYM4	ENST00000314607.11 linkuse as main transcript	c.937A>G	p.Thr313Ala	missense_variant	7/30	2	NM_005095.3	P1	Q5VZL5-1
ZMYM4	ENST00000457946.1 linkuse as main transcript	c.184A>G	p.Thr62Ala	missense_variant	3/24	5
ZMYM4	ENST00000482131.1 linkuse as main transcript	n.170A>G		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.000414

AC:

AN:

108620

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000381

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00462

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00262

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000350

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000393

AC:

AN:

221278

Hom.:

AF XY:

0.000338

AC XY:

AN XY:

121282

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000858

Gnomad NFE exome

AF:

0.000339

Gnomad OTH exome

AF:

0.000387

GnomAD4 exome

AF:

0.000268

AC:

314

AN:

1170158

Hom.:

Cov.:

AF XY:

0.000305

AC XY:

178

AN XY:

584432

show subpopulations

Gnomad4 AFR exome

AF:

0.0000510

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00519

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000814

Gnomad4 NFE exome

AF:

0.000171

Gnomad4 OTH exome

AF:

0.000332

GnomAD4 genome

AF:

0.000414

AC:

AN:

108620

Hom.:

Cov.:

AF XY:

0.000485

AC XY:

AN XY:

49488

show subpopulations

Gnomad4 AFR

AF:

0.0000381

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00462

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00262

Gnomad4 NFE

AF:

0.000350

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000400

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.000354

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2022

The c.937A>G (p.T313A) alteration is located in exon 7 (coding exon 7) of the ZMYM4 gene. This alteration results from a A to G substitution at nucleotide position 937, causing the threonine (T) at amino acid position 313 to be replaced by an alanine (A). 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

0.083

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.039

Eigen

Benign

-0.078

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.0038

MetaRNN

Benign

0.0088

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.63

REVEL

Benign

0.051

Sift

Uncertain

0.026

Sift4G

Benign

0.27

Polyphen

0.0010

Vest4

0.24

MVP

0.043

MPC

0.13

ClinPred

0.049

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.057

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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