Genetic Variant NM_006770.4:c.464T>A (chr2-118974336-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006770.4(MARCO):c.464T>A(p.Leu155His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MARCO
NM_006770.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0760

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006770.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCO	NM_006770.4	MANE Select	c.464T>A	p.Leu155His	missense	Exon 5 of 17	NP_006761.1	Q4ZG40

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MARCO	ENST00000327097.5	TSL:1 MANE Select	c.464T>A	p.Leu155His	missense	Exon 5 of 17	ENSP00000318916.4	Q9UEW3-1
MARCO	ENST00000874357.1		c.464T>A	p.Leu155His	missense	Exon 5 of 18	ENSP00000544416.1
MARCO	ENST00000958830.1		c.464T>A	p.Leu155His	missense	Exon 5 of 17	ENSP00000628889.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1442116

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715964

African (AFR)

AF:

0.00

AC:

AN:

33182

American (AMR)

AF:

0.00

AC:

AN:

42272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25694

East Asian (EAS)

AF:

0.00

AC:

AN:

39146

South Asian (SAS)

AF:

0.00

AC:

AN:

83220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52150

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101066

Other (OTH)

AF:

0.00

AC:

AN:

59638

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

0.010

BayesDel_noAF

Benign

-0.22

CADD

Benign

9.2

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.33

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.37

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.71

M_CAP

Uncertain

0.10

MetaRNN

Uncertain

0.61

MetaSVM

Uncertain

0.047

MutationAssessor

Benign

1.6

PhyloP100

-0.076

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.71

REVEL

Uncertain

0.34

Sift

Benign

0.16

Sift4G

Benign

0.41

Polyphen

1.0

Vest4

0.46

MutPred

0.46

Loss of catalytic residue at L155 (P = 0.0407)

MVP

0.88

MPC

0.35

ClinPred

0.21

GERP RS

1.9

Varity_R

0.048

gMVP

0.19

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over