Variant 20-58461514-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_153360.3(APCDD1L):c.782G>A(p.Arg261His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,445,678 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R261C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00078 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 3 hom. )

Consequence

APCDD1L
NM_153360.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.39

Variant links:

Genes affected

APCDD1L (HGNC:26892): (APC down-regulated 1 like) Predicted to enable Wnt-protein binding activity. Predicted to be involved in negative regulation of Wnt signaling pathway. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

APCDD1L links:

APCDD1L (HGNC:):

APCDD1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012780368).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APCDD1L	NM_153360.3 linkuse as main transcript	c.782G>A	p.Arg261His	missense_variant	4/4	ENST00000371149.8	NP_699191.1	Q8NCL9
APCDD1L	NM_001304787.2 linkuse as main transcript	c.815G>A	p.Arg272His	missense_variant	5/5		NP_001291716.1	Q8NCL9B4DDQ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APCDD1L	ENST00000371149.8 linkuse as main transcript	c.782G>A	p.Arg261His	missense_variant	4/4	1	NM_153360.3	ENSP00000360191.3		Q8NCL9
APCDD1L	ENST00000491015.1 linkuse as main transcript	n.193G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.000782

AC:

119

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000736

AC:

AN:

81540

Hom.:

AF XY:

0.000859

AC XY:

AN XY:

40738

show subpopulations

Gnomad AFR exome

AF:

0.000419

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000879

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00109

Gnomad OTH exome

AF:

0.000429

GnomAD4 exome

AF:

0.00122

AC:

1582

AN:

1293412

Hom.:

Cov.:

AF XY:

0.00116

AC XY:

728

AN XY:

625532

show subpopulations

Gnomad4 AFR exome

AF:

0.000526

Gnomad4 AMR exome

AF:

0.000859

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000284

Gnomad4 SAS exome

AF:

0.00133

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00138

Gnomad4 OTH exome

AF:

0.000919

GnomAD4 genome

AF:

0.000782

AC:

119

AN:

152266

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00118

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.000699

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.000992

AC:

ExAC

AF:

0.000379

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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 submitter

clinical testing

Ambry Genetics

Jan 31, 2024

The c.782G>A (p.R261H) alteration is located in exon 4 (coding exon 4) of the APCDD1L gene. This alteration results from a G to A substitution at nucleotide position 782, causing the arginine (R) at amino acid position 261 to be replaced by a histidine (H). 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

0.083

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.59

CADD

Benign

9.1

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.70

M_CAP

Benign

0.0087

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.052

Sift

Benign

0.049

Sift4G

Uncertain

0.044

Polyphen

0.45

Vest4

0.16

MVP

0.19

MPC

0.38

ClinPred

0.023

GERP RS

-1.9

Varity_R

0.066

gMVP

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over