4-48490607-G-A

Position:

• chr4-48490607-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000327939.4(ZAR1):​c.316G>A​(p.Val106Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000735 in 1,224,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000074 (0 hom.)
• Consequence: ZAR1 ENST00000327939.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.95

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.327291).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZAR1	NM_175619.3	c.316G>A	p.Val106Met	missense_variant	1/4	ENST00000327939.4	NP_783318.1
ZAR1	XR_007096396.1	n.356G>A		non_coding_transcript_exon_variant	1/6
ZAR1	XR_925129.4	n.356G>A		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZAR1	ENST00000327939.4	c.316G>A	p.Val106Met	missense_variant	1/4	1	NM_175619.3	ENSP00000329803	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000735 AC: 9 AN: 1224136 Hom.: 0 Cov.: 69 AF XY: 0.0000101 AC XY: 6 AN XY: 596542

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: 0.00000794

Gnomad4 OTH exome AF: 0.0000198

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 04, 2022

The c.316G>A (p.V106M) 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 316, causing the valine (V) at amino acid position 106 to be replaced by a methionine (M). 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	0.25
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.32
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.51	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	0.96	N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.21
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.036	D
Polyphen		1.0	D
Vest4		0.15
MutPred		0.16		Gain of MoRF binding (P = 0.0825);
MVP		0.055
MPC		1.7
ClinPred		0.77	D
GERP RS		1.4
Varity_R		0.095
gMVP		0.31

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.

Other links and lift over

hg19: chr4-48492624;