Variant rs975263 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_182762.4(MACC1):c.1544C>T(p.Ser515Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 1,613,700 control chromosomes in the GnomAD database, including 72,809 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.29 ( 7565 hom., cov: 32)

Exomes 𝑓: 0.28 ( 65244 hom. )

Consequence

MACC1
NM_182762.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.59

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0364147E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MACC1	NM_182762.4 linkuse as main transcript	c.1544C>T	p.Ser515Leu	missense_variant	5/7	ENST00000400331.10	NP_877439.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MACC1	ENST00000400331.10 linkuse as main transcript	c.1544C>T	p.Ser515Leu	missense_variant	5/7	2	NM_182762.4	ENSP00000383185	P1
MACC1	ENST00000332878.8 linkuse as main transcript	c.1544C>T	p.Ser515Leu	missense_variant	3/5	1		ENSP00000328410	P1
MACC1	ENST00000589011.1 linkuse as main transcript	c.1544C>T	p.Ser515Leu	missense_variant	3/5	5		ENSP00000466864	P1

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44646

AN:

151914

Hom.:

7563

Cov.:

show subpopulations

Gnomad AFR

AF:

0.294

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.803

Gnomad SAS

AF:

0.468

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.238

Gnomad OTH

AF:

0.281

GnomAD3 exomes

AF:

0.343

AC:

85974

AN:

250638

Hom.:

17899

AF XY:

0.342

AC XY:

46410

AN XY:

135508

show subpopulations

Gnomad AFR exome

AF:

0.293

Gnomad AMR exome

AF:

0.387

Gnomad ASJ exome

AF:

0.326

Gnomad EAS exome

AF:

0.818

Gnomad SAS exome

AF:

0.453

Gnomad FIN exome

AF:

0.284

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.295

GnomAD4 exome

AF:

0.277

AC:

405138

AN:

1461668

Hom.:

65244

Cov.:

AF XY:

0.282

AC XY:

205255

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.302

Gnomad4 AMR exome

AF:

0.377

Gnomad4 ASJ exome

AF:

0.323

Gnomad4 EAS exome

AF:

0.807

Gnomad4 SAS exome

AF:

0.450

Gnomad4 FIN exome

AF:

0.273

Gnomad4 NFE exome

AF:

0.238

Gnomad4 OTH exome

AF:

0.301

GnomAD4 genome

AF:

0.294

AC:

44684

AN:

152032

Hom.:

7565

Cov.:

AF XY:

0.302

AC XY:

22468

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.294

Gnomad4 AMR

AF:

0.332

Gnomad4 ASJ

AF:

0.323

Gnomad4 EAS

AF:

0.803

Gnomad4 SAS

AF:

0.468

Gnomad4 FIN

AF:

0.281

Gnomad4 NFE

AF:

0.238

Gnomad4 OTH

AF:

0.282

Alfa

AF:

0.265

Hom.:

15168

Bravo

AF:

0.298

TwinsUK

AF:

0.233

AC:

864

ALSPAC

AF:

0.237

AC:

912

ESP6500AA

AF:

0.290

AC:

1276

ESP6500EA

AF:

0.238

AC:

2048

ExAC

AF:

0.339

AC:

41097

Asia WGS

AF:

0.568

AC:

1978

AN:

3478

EpiCase

AF:

0.243

EpiControl

AF:

0.249

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.0076

T;T;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.76

.;.;T

MetaRNN

Benign

0.0000010

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L;L

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.7

N;N;.

REVEL

Benign

0.12

Sift

Benign

0.55

T;T;.

Sift4G

Benign

0.69

T;T;T

Polyphen

0.014

B;B;B

Vest4

0.022

MPC

0.013

ClinPred

0.0077

GERP RS

5.0

Varity_R

0.085

gMVP

0.21

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over