chr13-32311831-G-T

Position:

• chr13-32311831-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001136571.2(ZAR1L):​c.95C>A​(p.Pro32His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZAR1L NM_001136571.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.46

Genes affected

ZAR1L (HGNC:37116): (zygote arrest 1 like) This gene encodes a member of the ZAR1 family that is predominantly expressed in oocytes and early embryos. The protein may function as an RNA regulator in early embryos. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.082607955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZAR1L	NM_001136571.2	c.95C>A	p.Pro32His	missense_variant	3/6	ENST00000533490.7	NP_001130043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZAR1L	ENST00000533490.7	c.95C>A	p.Pro32His	missense_variant	3/6	5	NM_001136571.2	ENSP00000437289	P1
ZAR1L	ENST00000345108.6	c.95C>A	p.Pro32His	missense_variant	1/4	1		ENSP00000344616	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Jun 01, 2022

The c.95C>A (p.P32H) alteration is located in exon 1 (coding exon 1) of the ZAR1L gene. This alteration results from a C to A substitution at nucleotide position 95, causing the proline (P) at amino acid position 32 to be replaced by a histidine (H). 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	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.48	.;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.083	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.5	.;D
REVEL	Benign	0.052
Sift	Benign	0.058	.;T
Sift4G	Uncertain	0.013	D;D
Polyphen		0.12	B;B
Vest4		0.29
MutPred		0.20		Gain of catalytic residue at K30 (P = 0);Gain of catalytic residue at K30 (P = 0);
MVP		0.17
ClinPred		0.69	D
GERP RS		2.9
Varity_R		0.11
gMVP		0.26

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: chr13-32885968;