chr5-112707526-A-T

Position:

• chr5-112707526-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2 PP5 BP4

The NM_001407446.1(APC):​c.-192A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: APC NM_001407446.1 5_prime_UTR
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.40

Genes affected

APC (HGNC:583): (APC regulator of WNT signaling pathway) This gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. It is also involved in other processes including cell migration and adhesion, transcriptional activation, and apoptosis. Defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Mutations in the APC gene have been found to occur in most colorectal cancers, where disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. [provided by RefSeq, Jun 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-112707526-A-T is Pathogenic according to our data. Variant chr5-112707526-A-T is described in ClinVar as [Pathogenic]. Clinvar id is 243007.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APC	NM_001127511.3	c.-192A>T		5_prime_UTR_variant	1/14		NP_001120983.2
APC	NM_001354895.2	c.-375A>T		5_prime_UTR_variant	1/16		NP_001341824.1
APC	NM_001354897.2	c.-192A>T		5_prime_UTR_variant	1/15		NP_001341826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000507379.6	c.-192A>T		5_prime_UTR_variant	1/14	2		ENSP00000423224
APC	ENST00000509732.6	c.-142A>T		5_prime_UTR_variant	1/16	4		ENSP00000426541	P1
APC	ENST00000505350.2	c.-192A>T		5_prime_UTR_variant, NMD_transcript_variant	1/16	3		ENSP00000481752

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 5

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Familial adenomatous polyposis 1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jul 12, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Benign	0.96

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs879253784; hg19: chr5-112043223;