Genetic Variant ZMYM1:p.Val405Ile (chr1-35113043-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024772.5(ZMYM1):c.1213G>A(p.Val405Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

ZMYM1
NM_024772.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.391

Variant links:

Genes affected

ZMYM1 (HGNC:26253): (zinc finger MYM-type containing 1) Predicted to enable protein dimerization activity and zinc ion binding activity. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZMYM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034982085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYM1	NM_024772.5 link	c.1213G>A	p.Val405Ile	missense_variant	Exon 10 of 10	ENST00000359858.9	NP_079048.3	Q5SVZ6Q9H5R2B4DSJ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZMYM1	ENST00000359858.9 link	c.1213G>A	p.Val405Ile	missense_variant	Exon 10 of 10	1	NM_024772.5	ENSP00000352920.4		Q5SVZ6

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152104

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:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000161

AC:

AN:

248960

Hom.:

AF XY:

0.0000222

AC XY:

AN XY:

135088

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461436

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000130

Hom.:

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 01, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1213G>A (p.V405I) alteration is located in exon 10 (coding exon 9) of the ZMYM1 gene. This alteration results from a G to A substitution at nucleotide position 1213, causing the valine (V) at amino acid position 405 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

0.063

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.0012

T;.;T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.051

LIST_S2

Benign

0.35

.;T;T;.;.

M_CAP

Benign

0.0060

MetaRNN

Benign

0.035

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

N;.;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.040

.;N;.;N;N

REVEL

Benign

0.044

Sift

Benign

0.12

.;T;.;T;T

Sift4G

Benign

0.19

.;T;T;T;T

Polyphen

0.0050

B;.;B;B;B

Vest4

0.045, 0.043

MutPred

0.063

Gain of catalytic residue at P407 (P = 0.0879);Gain of catalytic residue at P407 (P = 0.0879);Gain of catalytic residue at P407 (P = 0.0879);Gain of catalytic residue at P407 (P = 0.0879);Gain of catalytic residue at P407 (P = 0.0879);

MVP

0.10

MPC

0.13

ClinPred

0.021

GERP RS

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.026

gMVP

0.040

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