Variant chr1-34987385-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_007167.4(ZMYM6):c.3697G>A(p.Glu1233Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 1,613,918 control chromosomes in the GnomAD database, including 1,460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.056 ( 710 hom., cov: 33)

Exomes 𝑓: 0.0093 ( 750 hom. )

Consequence

ZMYM6
NM_007167.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.987

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 Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014627576).

BP6

Variant 1-34987385-C-T is Benign according to our data. Variant chr1-34987385-C-T is described in ClinVar as [Benign]. Clinvar id is 3056816.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-34987385-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZMYM6	NM_007167.4 link	c.3697G>A	p.Glu1233Lys	missense_variant	16/16	ENST00000357182.9	NP_009098.3	O95789-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZMYM6	ENST00000357182.9 link	c.3697G>A	p.Glu1233Lys	missense_variant	16/16	1	NM_007167.4	ENSP00000349708.4	O95789-3
ZMYM6	ENST00000493328.5 link	n.5021G>A		non_coding_transcript_exon_variant	15/15	1
ENSG00000271741	ENST00000487874.1 link	n.2147-3438G>A		intron_variant		5		ENSP00000421752.1

Frequencies

GnomAD3 genomes

AF:

0.0562

AC:

8553

AN:

152148

Hom.:

707

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0246

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00411

Gnomad OTH

AF:

0.0378

GnomAD3 exomes

AF:

0.0182

AC:

4539

AN:

249210

Hom.:

308

AF XY:

0.0155

AC XY:

2093

AN XY:

135216

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.0126

Gnomad ASJ exome

AF:

0.0252

Gnomad EAS exome

AF:

0.00211

Gnomad SAS exome

AF:

0.0123

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00356

Gnomad OTH exome

AF:

0.0142

GnomAD4 exome

AF:

0.00927

AC:

13550

AN:

1461652

Hom.:

750

Cov.:

AF XY:

0.00881

AC XY:

6407

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.0141

Gnomad4 ASJ exome

AF:

0.0255

Gnomad4 EAS exome

AF:

0.00181

Gnomad4 SAS exome

AF:

0.0117

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.00312

Gnomad4 OTH exome

AF:

0.0190

GnomAD4 genome

AF:

0.0564

AC:

8584

AN:

152266

Hom.:

710

Cov.:

AF XY:

0.0547

AC XY:

4070

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.185

Gnomad4 AMR

AF:

0.0246

Gnomad4 ASJ

AF:

0.0233

Gnomad4 EAS

AF:

0.00174

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00412

Gnomad4 OTH

AF:

0.0374

Alfa

AF:

0.0264

Hom.:

175

Bravo

AF:

0.0636

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.170

AC:

617

ESP6500EA

AF:

0.00392

AC:

ExAC

AF:

0.0207

AC:

2503

Asia WGS

AF:

0.0170

AC:

AN:

3478

EpiCase

AF:

0.00387

EpiControl

AF:

0.00528

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ZMYM6-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 11, 2019

This variant is classified as 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

Benign

0.14

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.056

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

PrimateAI

Benign

0.45

PROVEAN

Benign

-2.2

REVEL

Benign

0.097

Sift

Uncertain

0.014

Sift4G

Pathogenic

0.0

Polyphen

0.70

Vest4

0.16

MPC

0.85

ClinPred

0.035

GERP RS

5.1

Varity_R

0.23

gMVP

0.69

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