rs149475817

Variant names:

• chr10-86452001-C-A
• NM_015045.5:c.3080G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-86452001-C-A
• chr10-86452001-C-G
• chr10-86452001-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015045.5(WAPL):​c.3080G>T​(p.Gly1027Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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. G1027D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: WAPL NM_015045.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.065457165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WAPL	NM_015045.5	c.3080G>T	p.Gly1027Val	missense_variant	Exon 15 of 19	ENST00000298767.10	NP_055860.1
WAPL	NM_001318328.2	c.3062G>T	p.Gly1021Val	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.3080G>T	p.Gly1027Val	missense_variant	Exon 15 of 19	1	NM_015045.5	ENSP00000298767.4
WAPL	ENST00000372075.2	c.807+1219G>T		intron_variant	Intron 6 of 9	2		ENSP00000361145.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461866 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.069	T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.15	.;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.065	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N;N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.58	N;.
REVEL	Benign	0.029
Sift	Benign	0.10	T;.
Sift4G	Benign	0.27	T;T
Polyphen		0.0	B;B
Vest4		0.12
MutPred		0.40		Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);
MVP		0.043
MPC		0.66
ClinPred		0.33	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.074
gMVP		0.075

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr10-88211758;