Variant chr1-52857112-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001004339.3(ZYG11A):c.371G>A(p.Arg124His) variant causes a missense change. The variant allele was found at a frequency of 0.00364 in 1,551,702 control chromosomes in the GnomAD database, including 135 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 60 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 75 hom. )

Consequence

ZYG11A
NM_001004339.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.38

Variant links:

Genes affected

ZYG11A (HGNC:32058): (zyg-11 family member A, cell cycle regulator) Predicted to be part of Cul2-RING ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ZYG11A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014766157).

BP6

Variant 1-52857112-G-A is Benign according to our data. Variant chr1-52857112-G-A is described in ClinVar as [Benign]. Clinvar id is 787746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZYG11A	NM_001004339.3 link	c.371G>A	p.Arg124His	missense_variant	3/14	ENST00000371528.2	NP_001004339.2	Q6WRX3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZYG11A	ENST00000371528.2 link	c.371G>A	p.Arg124His	missense_variant	3/14	5	NM_001004339.3	ENSP00000360583.1		Q6WRX3-1
ZYG11A	ENST00000371532.5 link	c.-19+2482G>A		intron_variant		5		ENSP00000360587.1		Q6WRX3-2

Frequencies

GnomAD3 genomes

AF:

0.0185

AC:

2812

AN:

152052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0632

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00925

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.0120

GnomAD3 exomes

AF:

0.00456

AC:

717

AN:

157176

Hom.:

AF XY:

0.00380

AC XY:

316

AN XY:

83138

show subpopulations

Gnomad AFR exome

AF:

0.0651

Gnomad AMR exome

AF:

0.00385

Gnomad ASJ exome

AF:

0.00658

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000307

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000345

Gnomad OTH exome

AF:

0.00338

GnomAD4 exome

AF:

0.00202

AC:

2827

AN:

1399532

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

1227

AN XY:

690270

show subpopulations

Gnomad4 AFR exome

AF:

0.0636

Gnomad4 AMR exome

AF:

0.00431

Gnomad4 ASJ exome

AF:

0.00596

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000316

Gnomad4 FIN exome

AF:

0.0000203

Gnomad4 NFE exome

AF:

0.000151

Gnomad4 OTH exome

AF:

0.00515

GnomAD4 genome

AF:

0.0185

AC:

2821

AN:

152170

Hom.:

Cov.:

AF XY:

0.0184

AC XY:

1368

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0633

Gnomad4 AMR

AF:

0.00923

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.0118

Alfa

AF:

0.00374

Hom.:

Bravo

AF:

0.0207

ESP6500AA

AF:

0.0556

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.00810

AC:

210

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 17, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.20

DEOGEN2

Benign

0.0016

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-2.5

PrimateAI

Benign

0.37

PROVEAN

Benign

1.6

REVEL

Benign

0.16

Sift

Benign

1.0

Sift4G

Benign

0.51

Polyphen

0.0

Vest4

0.077

MVP

0.014

ClinPred

0.0083

GERP RS

4.7

Varity_R

0.052

gMVP

0.25

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