Variant chr1-35359092-G-A 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.253G>A(p.Val85Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,613,668 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

ZMYM4
NM_005095.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.67

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:

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=0.041018844).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZMYM4	NM_005095.3 linkuse as main transcript	c.253G>A	p.Val85Ile	missense_variant	3/30	ENST00000314607.11
ZMYM4-AS1	NR_046659.1 linkuse as main transcript	n.189C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZMYM4	ENST00000314607.11 linkuse as main transcript	c.253G>A	p.Val85Ile	missense_variant	3/30	2	NM_005095.3	P1	Q5VZL5-1
ZMYM4-AS1	ENST00000432683.1 linkuse as main transcript	n.189C>T		non_coding_transcript_exon_variant	2/2	2
ZMYM4	ENST00000441447.1 linkuse as main transcript	c.157G>A	p.Val53Ile	missense_variant	4/4	5

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000836

AC:

AN:

251298

Hom.:

AF XY:

0.0000589

AC XY:

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000239

AC:

AN:

1461600

Hom.:

Cov.:

AF XY:

0.0000234

AC XY:

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152068

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.0000147

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000869

ExAC

AF:

0.0000824

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

Jan 19, 2024

The c.253G>A (p.V85I) alteration is located in exon 3 (coding exon 3) of the ZMYM4 gene. This alteration results from a G to A substitution at nucleotide position 253, causing the valine (V) at amino acid position 85 to be replaced by an isoleucine (I). 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

0.087

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.028

T;T

Eigen

Benign

-0.23

Eigen_PC

Benign

0.0097

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.85

T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.041

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

0.66

N;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

0.020

N;N

REVEL

Benign

0.040

Sift

Benign

0.27

T;T

Sift4G

Benign

0.56

T;D

Polyphen

0.011

B;.

Vest4

0.30

MVP

0.043

MPC

0.071

ClinPred

0.034

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.041

gMVP

0.10

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