13-32311289-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001136571.2(ZAR1L):​c.637C>T​(p.Arg213Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00004 in 1,548,444 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000039 ( 4 hom. )

Consequence

ZAR1L
NM_001136571.2 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.548
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.071593106).
BS2
High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZAR1LNM_001136571.2 linkuse as main transcriptc.637C>T p.Arg213Trp missense_variant 3/6 ENST00000533490.7 NP_001130043.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZAR1LENST00000533490.7 linkuse as main transcriptc.637C>T p.Arg213Trp missense_variant 3/65 NM_001136571.2 ENSP00000437289 P1
ZAR1LENST00000345108.6 linkuse as main transcriptc.637C>T p.Arg213Trp missense_variant 1/41 ENSP00000344616 P1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152164
Hom.:
0
Cov.:
32
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:
0.00633
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.0000132
AC:
2
AN:
151136
Hom.:
0
AF XY:
0.0000249
AC XY:
2
AN XY:
80266
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000409
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000444
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000387
AC:
54
AN:
1396162
Hom.:
4
Cov.:
31
AF XY:
0.0000407
AC XY:
28
AN XY:
688490
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000563
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000127
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000835
Gnomad4 OTH exome
AF:
0.0000173
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152282
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74448
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:
0.0000294
Gnomad4 OTH
AF:
0.000946
Bravo
AF:
0.0000189

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 submitterclinical testingAmbry GeneticsJun 07, 2024The c.637C>T (p.R213W) alteration is located in exon 1 (coding exon 1) of the ZAR1L gene. This alteration results from a C to T substitution at nucleotide position 637, causing the arginine (R) at amino acid position 213 to be replaced by a tryptophan (W). 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
0.096
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
16
DANN
Uncertain
1.0
DEOGEN2
Benign
0.10
T;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.040
N
LIST_S2
Benign
0.44
.;T
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.072
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.7
L;L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.40
T
PROVEAN
Uncertain
-2.9
.;D
REVEL
Benign
0.027
Sift
Uncertain
0.0080
.;D
Sift4G
Uncertain
0.010
D;D
Polyphen
0.013
B;B
Vest4
0.16
MutPred
0.34
Loss of disorder (P = 0.0101);Loss of disorder (P = 0.0101);
MVP
0.10
ClinPred
0.61
D
GERP RS
-4.6
Varity_R
0.073
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs867760006; hg19: chr13-32885426; COSMIC: COSV100563918; COSMIC: COSV100563918; API