rs762580615

Variant names:

• chr18-10471709-C-A
• rs762580615
• NM_153000.5:c.422C>A

Your query was ambiguous. Multiple possible variants found:

• chr18-10471709-C-A
• chr18-10471709-C-G
• chr18-10471709-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_153000.5(APCDD1):​c.422C>A​(p.Thr141Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. T141M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: APCDD1 NM_153000.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.52

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.873

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APCDD1	NM_153000.5	c.422C>A	p.Thr141Lys	missense_variant	Exon 3 of 5	ENST00000355285.10	NP_694545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APCDD1	ENST00000355285.10	c.422C>A	p.Thr141Lys	missense_variant	Exon 3 of 5	1	NM_153000.5	ENSP00000347433.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Pathogenic	27
DANN	Benign	0.96
DEOGEN2	Benign	0.25	T;T
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Pathogenic	3.0	M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-4.1	D;.
REVEL	Uncertain	0.49
Sift	Uncertain	0.0040	D;.
Sift4G	Uncertain	0.0040	D;D
Polyphen		1.0	D;.
Vest4		0.95
MutPred		0.65		Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);
MVP		0.61
MPC		1.1
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.66
gMVP		0.83

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: rs762580615; hg19: chr18-10471706;