10-86446431-G-C

Variant names:

• chr10-86446431-G-C
• rs113314659
• NM_015045.5:c.3133C>G

Variant summary

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

The NM_015045.5(WAPL):​c.3133C>G​(p.Arg1045Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1045W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WAPL NM_015045.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.95

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]

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=0.24836087).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WAPL	NM_015045.5	c.3133C>G	p.Arg1045Gly	missense_variant	Exon 16 of 19	ENST00000298767.10	NP_055860.1
WAPL	NM_001318328.2	c.3115C>G	p.Arg1039Gly	missense_variant	Exon 16 of 19		NP_001305257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WAPL	ENST00000298767.10	c.3133C>G	p.Arg1045Gly	missense_variant	Exon 16 of 19	1	NM_015045.5	ENSP00000298767.4
WAPL	ENST00000372075.2	c.826C>G	p.Arg276Gly	missense_variant	Exon 7 of 10	2		ENSP00000361145.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.061	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;T;T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.044
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	.;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.0	L;L;.;.
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.5	D;.;D;.
REVEL	Benign	0.21
Sift	Benign	0.072	T;.;T;.
Sift4G	Benign	0.093	T;T;T;.
Polyphen		0.45	B;B;.;.
Vest4		0.68
MutPred		0.28		Loss of stability (P = 0.0883);Loss of stability (P = 0.0883);.;.;
MVP		0.28
MPC		1.5
ClinPred		0.94	D
GERP RS		1.5
Varity_R		0.29
gMVP		0.28

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

Other links and lift over

dbSNP: rs113314659; hg19: chr10-88206188;