Variant 1-52857673-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001004339.3(ZYG11A):c.932C>T(p.Pro311Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000644 in 1,552,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

ZYG11A
NM_001004339.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.41

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 Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.836

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZYG11A	NM_001004339.3 link	c.932C>T	p.Pro311Leu	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.932C>T	p.Pro311Leu	missense_variant	3/14	5	NM_001004339.3	ENSP00000360583.1		Q6WRX3-1
ZYG11A	ENST00000371532.5 link	c.-19+3043C>T		intron_variant		5		ENSP00000360587.1		Q6WRX3-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000189

AC:

AN:

158394

Hom.:

AF XY:

0.0000240

AC XY:

AN XY:

83506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000809

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:

0.000222

GnomAD4 exome

AF:

0.00000571

AC:

AN:

1399888

Hom.:

Cov.:

AF XY:

0.00000579

AC XY:

AN XY:

690406

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000140

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:

9.27e-7

Gnomad4 OTH exome

AF:

0.0000344

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

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:

0.0000282

Hom.:

Bravo

AF:

0.0000453

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 23, 2024

The c.932C>T (p.P311L) alteration is located in exon 3 (coding exon 3) of the ZYG11A gene. This alteration results from a C to T substitution at nucleotide position 932, causing the proline (P) at amino acid position 311 to be replaced by a leucine (L). 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

0.19

BayesDel_addAF

Benign

-0.072

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Pathogenic

0.71

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.051

MetaRNN

Pathogenic

0.84

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.6

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-6.3

REVEL

Uncertain

0.42

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.031

Polyphen

1.0

Vest4

0.68

MutPred

0.59

Gain of helix (P = 0.062);

MVP

0.50

ClinPred

0.95

GERP RS

5.3

Varity_R

0.38

gMVP

0.63

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