rs147394539

Variant names:

• chr5-112838441-G-A
• NM_000038.6:c.2847G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-112838441-G-A
• chr5-112838441-G-C
• chr5-112838441-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_000038.6(APC):​c.2847G>A​(p.Met949Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: APC NM_000038.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.52

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]

ENSG00000258864 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 5-112838441-G-A is Benign according to our data. Variant chr5-112838441-G-A is described in ClinVar as [Benign]. Clinvar id is 3713342.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APC	NM_000038.6	c.2847G>A	p.Met949Ile	missense_variant	Exon 16 of 16	ENST00000257430.9	NP_000029.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APC	ENST00000257430.9	c.2847G>A	p.Met949Ile	missense_variant	Exon 16 of 16	5	NM_000038.6	ENSP00000257430.4
ENSG00000258864	ENST00000520401.1	n.228+9469G>A		intron_variant	Intron 3 of 7	3		ENSP00000454861.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial adenomatous polyposis 1 Benign:1

Jul 02, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Uncertain	0.54	.;D;D;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T;.;T;T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.46	T;T;T;T
MetaSVM	Benign	-0.37	T
MutationAssessor	Benign	0.69	.;N;N;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.090	N;N;N;N
REVEL	Uncertain	0.47
Sift	Benign	0.13	T;T;T;T
Sift4G	Benign	0.29	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.66, 0.28
MutPred		0.75		.;Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);
MVP		0.99
ClinPred		0.13	T
GERP RS		3.1
Varity_R		0.071
gMVP		0.24

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.

Other links and lift over

hg19: chr5-112174138; COSMIC: COSV99970545; COSMIC: COSV99970545;