Variant 18-10471719-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153000.5(APCDD1):c.432C>G(p.Asp144Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,800 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

APCDD1
NM_153000.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01

Variant links:

Genes affected

APCDD1 (HGNC:15718): (APC down-regulated 1) This locus encodes an inhibitor of the Wnt signaling pathway. Mutations at this locus have been associated with hereditary hypotrichosis simplex. Increased expression of this gene may also be associated with colorectal carcinogenesis.[provided by RefSeq, Sep 2010]

APCDD1 links:

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ACMG classification

Classification made for transcript

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=0.23583165).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APCDD1	NM_153000.5 linkuse as main transcript	c.432C>G	p.Asp144Glu	missense_variant	3/5	ENST00000355285.10	NP_694545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
APCDD1	ENST00000355285.10 linkuse as main transcript	c.432C>G	p.Asp144Glu	missense_variant	3/5	1	NM_153000.5	ENSP00000347433	P1
APCDD1	ENST00000578882.1 linkuse as main transcript	c.432C>G	p.Asp144Glu	missense_variant	3/5	3		ENSP00000463104
APCDD1	ENST00000423585.2 linkuse as main transcript	c.59-13743C>G		intron_variant, NMD_transcript_variant		3		ENSP00000404930
APCDD1	ENST00000582723.1 linkuse as main transcript	c.*179C>G		3_prime_UTR_variant, NMD_transcript_variant	2/3	3		ENSP00000463110

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727202

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 30, 2024

The c.432C>G (p.D144E) alteration is located in exon 3 (coding exon 3) of the APCDD1 gene. This alteration results from a C to G substitution at nucleotide position 432, causing the aspartic acid (D) at amino acid position 144 to be replaced by a glutamic acid (E). 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.035

T;T

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.022

FATHMM_MKL

Uncertain

0.84

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.0062

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.52

N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.7

N;.

REVEL

Benign

0.050

Sift

Benign

0.43

T;.

Sift4G

Benign

0.59

T;T

Polyphen

0.086

B;.

Vest4

0.15

MutPred

0.49

Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);

MVP

0.48

MPC

0.31

ClinPred

0.50

GERP RS

4.4

Varity_R

0.15

gMVP

0.30

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over