Variant 4-48490703-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000327939.4(ZAR1):c.412G>A(p.Ala138Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000332 in 1,325,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

ZAR1
ENST00000327939.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.11

Variant links:

Genes affected

ZAR1 (HGNC:20436): (zygote arrest 1) This maternal effect gene is oocyte-specific and encodes a protein that is thought to function in the initiation of embryogenesis. A similar protein in mouse is required for female fertility. [provided by RefSeq, Jul 2013]

ZAR1 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=0.039705455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZAR1	NM_175619.3 linkuse as main transcript	c.412G>A	p.Ala138Thr	missense_variant	1/4	ENST00000327939.4	NP_783318.1
ZAR1	XR_007096396.1 linkuse as main transcript	n.452G>A		non_coding_transcript_exon_variant	1/6
ZAR1	XR_925129.4 linkuse as main transcript	n.452G>A		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZAR1	ENST00000327939.4 linkuse as main transcript	c.412G>A	p.Ala138Thr	missense_variant	1/4	1	NM_175619.3	ENSP00000329803	P1

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

151758

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000701

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

AF:

0.0000128

AC:

AN:

1173598

Hom.:

Cov.:

AF XY:

0.0000141

AC XY:

AN XY:

566546

show subpopulations

Gnomad4 AFR exome

AF:

0.000383

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000361

Gnomad4 NFE exome

AF:

0.00000308

Gnomad4 OTH exome

AF:

0.0000209

GnomAD4 genome

AF:

0.000191

AC:

AN:

151866

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74244

show subpopulations

Gnomad4 AFR

AF:

0.000699

Gnomad4 AMR

AF:

0.00

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:

0.000147

ExAC

AF:

0.0000132

AC:

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 06, 2023

The c.412G>A (p.A138T) alteration is located in exon 1 (coding exon 1) of the ZAR1 gene. This alteration results from a G to A substitution at nucleotide position 412, causing the alanine (A) at amino acid position 138 to be replaced by a threonine (T). 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

0.088

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.75

CADD

Benign

4.6

DANN

Benign

0.97

DEOGEN2

Benign

0.072

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.36

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.87

REVEL

Benign

0.023

Sift

Benign

0.28

Sift4G

Benign

0.36

Polyphen

0.010

Vest4

0.019

MVP

0.014

MPC

0.71

ClinPred

0.14

GERP RS

0.15

Varity_R

0.061

gMVP

0.13

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