Genetic Variant ZMYM4:p.Ala263Thr (chr1-35361736-G-A) – 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.787G>A(p.Ala263Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000185 in 1,461,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ZMYM4
NM_005095.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.80

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:

ZMYM4-AS1 (HGNC:40624): (ZMYM4 antisense RNA 1)

ZMYM4-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17885602).

BS2

High AC in GnomAdExome4 at 27 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYM4	NM_005095.3 link	c.787G>A	p.Ala263Thr	missense_variant	Exon 5 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.787G>A	p.Ala263Thr	missense_variant	Exon 5 of 30	2	NM_005095.3	ENSP00000322915.6	Q5VZL5-1
ZMYM4	ENST00000457946.1 link	c.31G>A	p.Ala11Thr	missense_variant	Exon 1 of 24	5		ENSP00000400506.1	H7C1I7
ZMYM4	ENST00000482131.1 link	n.20G>A		non_coding_transcript_exon_variant	Exon 1 of 3	2
ZMYM4-AS1	ENST00000432683.1 link	n.113-2568C>T		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

251030

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135700

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461448

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727050

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000234

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 31, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.787G>A (p.A263T) alteration is located in exon 5 (coding exon 5) of the ZMYM4 gene. This alteration results from a G to A substitution at nucleotide position 787, causing the alanine (A) at amino acid position 263 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

0.11

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.075

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.74

M_CAP

Benign

0.012

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.52

MutationAssessor

Benign

0.69

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.4

REVEL

Benign

0.14

Sift

Benign

0.030

Sift4G

Benign

0.15

Polyphen

0.26

Vest4

0.36

MutPred

0.11

Gain of phosphorylation at A263 (P = 0.0339);

MVP

0.093

MPC

0.12

ClinPred

0.22

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.40

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