GeneBe

rs36106647

Positions:

Variant summary

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

The NM_182762.4(MACC1):​c.2011_2012insC​(p.Leu671ProfsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Consequence

MACC1
NM_182762.4 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.28
Variant links:
Genes affected
MACC1 (HGNC:30215): (MET transcriptional regulator MACC1) MACC1 is a key regulator of the hepatocyte growth factor (HGF; MIM 142409)-HGF receptor (HGFR, or MET; MIM 164860) pathway, which is involved in cellular growth, epithelial-mesenchymal transition, angiogenesis, cell motility, invasiveness, and metastasis. Expression of MACC1 in colon cancer (MIM 114500) specimens is an independent prognostic indicator for metastasis formation and metastasis-free survival (Stein et al., 2009 [PubMed 19098908]).[supplied by OMIM, Mar 2009]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MACC1NM_182762.4 linkuse as main transcriptc.2011_2012insC p.Leu671ProfsTer12 frameshift_variant 5/7 ENST00000400331.10 NP_877439.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MACC1ENST00000400331.10 linkuse as main transcriptc.2011_2012insC p.Leu671ProfsTer12 frameshift_variant 5/72 NM_182762.4 ENSP00000383185 P1
MACC1ENST00000332878.8 linkuse as main transcriptc.2011_2012insC p.Leu671ProfsTer12 frameshift_variant 3/51 ENSP00000328410 P1
MACC1ENST00000589011.1 linkuse as main transcriptc.2011_2012insC p.Leu671ProfsTer12 frameshift_variant 3/55 ENSP00000466864 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs36106647; hg19: chr7-20197972; API