2-118981485-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006770.4(MARCO):c.843C>A(p.Asp281Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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)
• Consequence: MARCO NM_006770.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0320

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]

ACMG classification

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=0.17156333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARCO	NM_006770.4	c.843C>A	p.Asp281Glu	missense_variant	9/17	ENST00000327097.5
MARCO	XM_011512082.3	c.843C>A	p.Asp281Glu	missense_variant	9/17
MARCO	XM_011512083.4	c.480C>A	p.Asp160Glu	missense_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARCO	ENST00000327097.5	c.843C>A	p.Asp281Glu	missense_variant	9/17	1	NM_006770.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 10, 2023

The c.843C>A (p.D281E) alteration is located in exon 9 (coding exon 9) of the MARCO gene. This alteration results from a C to A substitution at nucleotide position 843, causing the aspartic acid (D) at amino acid position 281 to be replaced by a glutamic acid (E). 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	0.23
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
Cadd	Benign	12
Dann	Benign	0.36
DEOGEN2	Benign	0.091	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.063	N
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.32	T
MutationAssessor	Benign	-0.59	N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.29
Sift	Benign	0.49	T
Sift4G	Benign	0.71	T
Polyphen		0.97	D
Vest4		0.29
MutPred		0.19		Loss of catalytic residue at D281 (P = 0.1302);
MVP		0.78
MPC		0.31
ClinPred		0.33	T
GERP RS		-0.070
Varity_R		0.040
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-119739061;