chr10-86452068-T-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

The NM_015045.5(WAPL):ā€‹c.3013A>Gā€‹(p.Met1005Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000616 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000062 ( 0 hom. )

Consequence

WAPL
NM_015045.5 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.80
Variant links:
Genes affected
WAPL (HGNC:23293): (WAPL cohesin release factor) Involved in several processes, including negative regulation of DNA replication; negative regulation of chromatin binding activity; and regulation of sister chromatid cohesion. Located in several cellular components, including Golgi apparatus; intercellular bridge; and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), WAPL. . Gene score misZ 3.4597 (greater than the threshold 3.09). Trascript score misZ 4.2731 (greater than threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder.
BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WAPLNM_015045.5 linkuse as main transcriptc.3013A>G p.Met1005Val missense_variant 15/19 ENST00000298767.10
WAPLNM_001318328.2 linkuse as main transcriptc.2995A>G p.Met999Val missense_variant 15/19

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WAPLENST00000298767.10 linkuse as main transcriptc.3013A>G p.Met1005Val missense_variant 15/191 NM_015045.5 P1Q7Z5K2-1
WAPLENST00000372075.2 linkuse as main transcriptc.807+1152A>G intron_variant 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251480
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461884
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.000149
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000189
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

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 09, 2022The c.3013A>G (p.M1005V) alteration is located in exon 15 (coding exon 14) of the WAPL gene. This alteration results from a A to G substitution at nucleotide position 3013, causing the methionine (M) at amino acid position 1005 to be replaced by a valine (V). 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
0.30
BayesDel_addAF
Benign
-0.036
T
BayesDel_noAF
Uncertain
-0.050
CADD
Uncertain
23
DANN
Benign
0.97
DEOGEN2
Benign
0.10
T;T
Eigen
Uncertain
0.27
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.93
.;D
M_CAP
Benign
0.022
T
MetaRNN
Uncertain
0.51
D;D
MetaSVM
Benign
-0.86
T
MutationAssessor
Benign
0.92
L;L
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-1.1
N;.
REVEL
Benign
0.18
Sift
Benign
0.12
T;.
Sift4G
Benign
0.26
T;T
Polyphen
0.084
B;B
Vest4
0.81
MutPred
0.44
Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP
0.38
MPC
1.2
ClinPred
0.20
T
GERP RS
5.8
Varity_R
0.39
gMVP
0.46

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.

Other links and lift over

dbSNP: rs779199618; hg19: chr10-88211825; API