Genetic Variant ZMYM6:p.Leu1022Ser (chr1-34988017-A-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_007167.4(ZMYM6):c.3065T>C(p.Leu1022Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000069 in 1,551,378 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

ZMYM6
NM_007167.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.23

Variant links:

Genes affected

ZMYM6 (HGNC:13050): (zinc finger MYM-type containing 6) Predicted to enable DNA binding activity. Involved in cytoskeleton organization and regulation of cell morphogenesis. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZMYM6 links:

ENSG00000271741 (HGNC:):

ENSG00000271741 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.034664184).

BP6

Variant 1-34988017-A-G is Benign according to our data. Variant chr1-34988017-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3052001.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZMYM6	NM_007167.4 link	c.3065T>C	p.Leu1022Ser	missense_variant	Exon 16 of 16	ENST00000357182.9	NP_009098.3	O95789-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZMYM6	ENST00000357182.9 link	c.3065T>C	p.Leu1022Ser	missense_variant	Exon 16 of 16	1	NM_007167.4	ENSP00000349708.4	O95789-3
ZMYM6	ENST00000493328.5 link	n.4389T>C		non_coding_transcript_exon_variant	Exon 15 of 15	1
ENSG00000271741	ENST00000487874.1 link	n.2147-4070T>C		intron_variant	Intron 15 of 16	5		ENSP00000421752.1

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000561

AC:

AN:

151630

Hom.:

AF XY:

0.000435

AC XY:

AN XY:

80454

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00341

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:

0.00

Gnomad OTH exome

AF:

0.000232

GnomAD4 exome

AF:

0.0000700

AC:

AN:

1399084

Hom.:

Cov.:

AF XY:

0.0000623

AC XY:

AN XY:

690002

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00269

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:

0.00

Gnomad4 OTH exome

AF:

0.0000345

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000166

ExAC

AF:

0.0000449

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ZMYM6-related disorder

Benign:1

May 23, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.61

M_CAP

Benign

0.053

MetaRNN

Benign

0.035

MetaSVM

Benign

-0.89

MutationAssessor

Uncertain

2.5

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.21

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.024

Polyphen

1.0

Vest4

0.60

MutPred

0.66

Gain of disorder (P = 0.0125);

MVP

0.36

MPC

0.63

ClinPred

0.27

GERP RS

4.2

Varity_R

0.39

gMVP

0.65

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