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. The variant received 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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• hypotrichosis 1

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• hypotrichosis simplex

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000301982 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153000.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APCDD1	NM_153000.5	MANE Select	c.422C>A	p.Thr141Lys	missense	Exon 3 of 5	NP_694545.1	Q8J025

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APCDD1	ENST00000355285.10	TSL:1 MANE Select	c.422C>A	p.Thr141Lys	missense	Exon 3 of 5	ENSP00000347433.4	Q8J025
	APCDD1	ENST00000578882.1	TSL:3	c.422C>A	p.Thr141Lys	missense	Exon 3 of 5	ENSP00000463104.1	J3KTQ6
	APCDD1	ENST00000582723.1	TSL:3	n.*169C>A		non_coding_transcript_exon	Exon 2 of 3	ENSP00000463110.1	J3KTR1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.80
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Pathogenic	3.0	M
PhyloP100		7.5
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.49
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.65		Gain of solvent accessibility (P = 0.012)
MVP		0.61
MPC		1.1
ClinPred		0.99	D
GERP RS		5.3
PromoterAI		-0.015	Neutral
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

Other links and lift over

dbSNP: rs762580615; hg19: chr18-10471706;