Variant chr2-118974560-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006770.4(MARCO):c.608A>T(p.Glu203Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000558 in 1,612,144 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

MARCO
NM_006770.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.24

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MARCO	NM_006770.4 linkuse as main transcript	c.608A>T	p.Glu203Val	missense_variant	6/17	ENST00000327097.5	NP_006761.1
MARCO	XM_011512082.3 linkuse as main transcript	c.608A>T	p.Glu203Val	missense_variant	6/17		XP_011510384.1
MARCO	XM_011512083.4 linkuse as main transcript	c.245A>T	p.Glu82Val	missense_variant	3/14		XP_011510385.1
MARCO	XM_017005171.3 linkuse as main transcript	c.608A>T	p.Glu203Val	missense_variant	6/9		XP_016860660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MARCO	ENST00000327097.5 linkuse as main transcript	c.608A>T	p.Glu203Val	missense_variant	6/17	1	NM_006770.4	ENSP00000318916	P1	Q9UEW3-1

Frequencies

GnomAD3 genomes

AF:

0.0000331

AC:

AN:

151224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000843

AC:

AN:

249026

Hom.:

AF XY:

0.0000891

AC XY:

AN XY:

134724

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000349

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:

0.0000621

Gnomad OTH exome

AF:

0.000332

GnomAD4 exome

AF:

0.0000582

AC:

AN:

1460920

Hom.:

Cov.:

AF XY:

0.0000619

AC XY:

AN XY:

726742

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000493

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:

0.0000450

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000331

AC:

AN:

151224

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73782

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.0000659

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Jul 25, 2023

The c.608A>T (p.E203V) alteration is located in exon 6 (coding exon 6) of the MARCO gene. This alteration results from a A to T substitution at nucleotide position 608, causing the glutamic acid (E) at amino acid position 203 to be replaced by a valine (V). 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

0.17

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Uncertain

0.62

Eigen

Benign

-0.0080

Eigen_PC

Benign

-0.0080

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.11

MetaRNN

Uncertain

0.46

MetaSVM

Uncertain

0.20

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.83

N;N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.43

Sift

Uncertain

0.0050

Sift4G

Benign

0.15

Polyphen

0.91

Vest4

0.39

MutPred

0.31

Gain of ubiquitination at K201 (P = 0.1693);

MVP

0.96

MPC

0.067

ClinPred

0.22

GERP RS

2.5

Varity_R

0.26

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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