10-86451987-C-T

Variant names:

• chr10-86451987-C-T
• NM_015045.5:c.3094G>A

Variant summary

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

The NM_015045.5(WAPL):​c.3094G>A​(p.Ala1032Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WAPL NM_015045.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.54

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WAPL	NM_015045.5	c.3094G>A	p.Ala1032Thr	missense_variant	Exon 15 of 19	ENST00000298767.10	NP_055860.1
WAPL	NM_001318328.2	c.3076G>A	p.Ala1026Thr	missense_variant	Exon 15 of 19		NP_001305257.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WAPL	ENST00000298767.10	c.3094G>A	p.Ala1032Thr	missense_variant	Exon 15 of 19	1	NM_015045.5	ENSP00000298767.4
WAPL	ENST00000372075.2	c.807+1233G>A		intron_variant	Intron 6 of 9	2		ENSP00000361145.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3094G>A (p.A1032T) alteration is located in exon 15 (coding exon 14) of the WAPL gene. This alteration results from a G to A substitution at nucleotide position 3094, causing the alanine (A) at amino acid position 1032 to be replaced by a threonine (T). 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	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.45	T;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Benign	0.27
Sift	Benign	0.042	D;.
Sift4G	Benign	0.070	T;T
Polyphen		0.90	P;P
Vest4		0.85
MutPred		0.36		Gain of loop (P = 0.2045);Gain of loop (P = 0.2045);
MVP		0.30
MPC		1.4
ClinPred		0.96	D
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.59
gMVP		0.40

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: chr10-88211744;