Variant 4-48490335-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000327939.4(ZAR1):c.44C>G(p.Pro15Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000441 in 1,361,712 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P15L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000044 ( 0 hom. )

Consequence

ZAR1
ENST00000327939.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.60

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:

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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, 0.758

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZAR1	NM_175619.3 linkuse as main transcript	c.44C>G	p.Pro15Arg	missense_variant	1/4	ENST00000327939.4	NP_783318.1
ZAR1	XR_007096396.1 linkuse as main transcript	n.84C>G		non_coding_transcript_exon_variant	1/6
ZAR1	XR_925129.4 linkuse as main transcript	n.84C>G		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.44C>G	p.Pro15Arg	missense_variant	1/4	1	NM_175619.3	ENSP00000329803	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000441

AC:

AN:

1361712

Hom.:

Cov.:

AF XY:

0.00000743

AC XY:

AN XY:

672842

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000561

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 17, 2023

The c.44C>G (p.P15R) alteration is located in exon 1 (coding exon 1) of the ZAR1 gene. This alteration results from a C to G substitution at nucleotide position 44, causing the proline (P) at amino acid position 15 to be replaced by an arginine (R). 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

0.18

BayesDel_addAF

Uncertain

0.050

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Benign

0.0094

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.43

M_CAP

Pathogenic

0.63

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.94

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.16

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.0060

Polyphen

0.99

Vest4

0.61

MutPred

0.46

Gain of catalytic residue at P15 (P = 0.0145);

MVP

0.067

MPC

1.7

ClinPred

0.97

GERP RS

3.5

Varity_R

0.23

gMVP

0.40

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over