Genetic Variant ZMYM4:p.Ala321Val (chr1-35370408-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_005095.3(ZMYM4):c.962C>T(p.Ala321Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000398 in 1,505,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000080 ( 0 hom., cov: 27)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

ZMYM4
NM_005095.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.93

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12882245).

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYM4	NM_005095.3 link	c.962C>T	p.Ala321Val	missense_variant	Exon 7 of 30	ENST00000314607.11	NP_005086.2	Q5VZL5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZMYM4	ENST00000314607.11 link	c.962C>T	p.Ala321Val	missense_variant	Exon 7 of 30	2	NM_005095.3	ENSP00000322915.6	Q5VZL5-1
ZMYM4	ENST00000457946.1 link	c.206C>T	p.Ala69Val	missense_variant	Exon 3 of 24	5		ENSP00000400506.1	H7C1I7
ZMYM4	ENST00000482131.1 link	n.195C>T		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.00000799

AC:

AN:

125220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000154

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248002

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134454

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 SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000362

AC:

AN:

1380534

Hom.:

Cov.:

AF XY:

0.00000437

AC XY:

AN XY:

687244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000281

Gnomad4 OTH exome

AF:

0.0000184

GnomAD4 genome

AF:

0.00000798

AC:

AN:

125268

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

58586

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000154

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000615

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.962C>T (p.A321V) alteration is located in exon 7 (coding exon 7) of the ZMYM4 gene. This alteration results from a C to T substitution at nucleotide position 962, causing the alanine (A) at amino acid position 321 to be replaced by a valine (V). 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

0.10

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

Eigen

Benign

0.19

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.0064

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.53

REVEL

Benign

0.062

Sift

Benign

0.10

Sift4G

Benign

0.24

Polyphen

0.89

Vest4

0.28

MVP

0.043

MPC

0.092

ClinPred

0.44

GERP RS

4.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.33

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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