Variant 7-20141117-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_182762.4(MACC1):c.2388T>G(p.Ser796Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,458,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

MACC1
NM_182762.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.610

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]

MACC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26859745).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACC1	NM_182762.4 linkuse as main transcript	c.2388T>G	p.Ser796Arg	missense_variant	7/7	ENST00000400331.10	NP_877439.3	Q6ZN28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MACC1	ENST00000400331.10 linkuse as main transcript	c.2388T>G	p.Ser796Arg	missense_variant	7/7	2	NM_182762.4	ENSP00000383185.3	Q6ZN28
MACC1	ENST00000332878.8 linkuse as main transcript	c.2388T>G	p.Ser796Arg	missense_variant	5/5	1		ENSP00000328410.4	Q6ZN28
MACC1	ENST00000589011.1 linkuse as main transcript	c.2388T>G	p.Ser796Arg	missense_variant	5/5	5		ENSP00000466864.1	Q6ZN28

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

247874

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134212

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1458972

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725798

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 14, 2024

The c.2388T>G (p.S796R) alteration is located in exon 7 (coding exon 4) of the MACC1 gene. This alteration results from a T to G substitution at nucleotide position 2388, causing the serine (S) at amino acid position 796 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.56

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.43

CADD

Benign

5.4

DANN

Uncertain

0.98

DEOGEN2

Benign

0.089

T;T;T

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.85

.;.;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.2

M;M;M

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.3

N;N;.

REVEL

Benign

0.22

Sift

Uncertain

0.015

D;D;.

Sift4G

Uncertain

0.023

D;D;D

Polyphen

0.94

P;P;P

Vest4

0.41

MutPred

0.58

Gain of MoRF binding (P = 0.0494);Gain of MoRF binding (P = 0.0494);Gain of MoRF binding (P = 0.0494);

MVP

0.12

MPC

0.046

ClinPred

0.83

GERP RS

-7.2

Varity_R

0.19

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over