Variant chr2-118974381-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006770.4(MARCO):c.509C>G(p.Pro170Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,610,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P170L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

MARCO
NM_006770.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.597

Variant links:

Genes affected

MARCO (HGNC:6895): (macrophage receptor with collagenous structure) The protein encoded by this gene is a member of the class A scavenger receptor family and is part of the innate antimicrobial immune system. The protein may bind both Gram-negative and Gram-positive bacteria via an extracellular, C-terminal, scavenger receptor cysteine-rich (SRCR) domain. In addition to short cytoplasmic and transmembrane domains, there is an extracellular spacer domain and a long, extracellular collagenous domain. The protein may form a trimeric molecule by the association of the collagenous domains of three identical polypeptide chains. [provided by RefSeq, Jul 2008]

MARCO links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11737648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MARCO	NM_006770.4 linkuse as main transcript	c.509C>G	p.Pro170Arg	missense_variant	5/17	ENST00000327097.5
MARCO	XM_011512082.3 linkuse as main transcript	c.509C>G	p.Pro170Arg	missense_variant	5/17
MARCO	XM_011512083.4 linkuse as main transcript	c.146C>G	p.Pro49Arg	missense_variant	2/14
MARCO	XM_017005171.3 linkuse as main transcript	c.509C>G	p.Pro170Arg	missense_variant	5/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARCO	ENST00000327097.5 linkuse as main transcript	c.509C>G	p.Pro170Arg	missense_variant	5/17	1	NM_006770.4	P1	Q9UEW3-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000824

AC:

AN:

242742

Hom.:

AF XY:

0.0000228

AC XY:

AN XY:

131408

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000560

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:

0.00000911

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1458674

Hom.:

Cov.:

AF XY:

0.00000965

AC XY:

AN XY:

725238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000519

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000264

ExAC

AF:

0.0000659

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 12, 2021

The c.509C>G (p.P170R) alteration is located in exon 5 (coding exon 5) of the MARCO gene. This alteration results from a C to G substitution at nucleotide position 509, causing the proline (P) at amino acid position 170 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

Benign

0.099

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.19

CADD

Benign

0.18

DANN

Benign

0.45

DEOGEN2

Uncertain

0.57

Eigen

Benign

-0.91

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.094

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.041

MetaRNN

Benign

0.12

MetaSVM

Uncertain

0.073

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.42

Sift

Benign

0.41

Sift4G

Benign

0.56

Polyphen

0.66

Vest4

0.27

MutPred

0.49

Gain of methylation at P170 (P = 0.009);

MVP

0.71

MPC

0.30

ClinPred

0.073

GERP RS

-0.018

Varity_R

0.025

gMVP

0.097

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over