2-118942319-C-A

Variant names:

• chr2-118942319-C-A
• NM_006770.4:c.19C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006770.4(MARCO):​c.19C>A​(p.Leu7Ile) 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. 17/22 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)
• Consequence: MARCO NM_006770.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.122
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20330536).

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.19C>A	p.Leu7Ile	missense	Exon 1 of 17	NP_006761.1	Q4ZG40

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARCO	ENST00000327097.5	TSL:1 MANE Select	c.19C>A	p.Leu7Ile	missense	Exon 1 of 17	ENSP00000318916.4	Q9UEW3-1
	MARCO	ENST00000874357.1		c.19C>A	p.Leu7Ile	missense	Exon 1 of 18	ENSP00000544416.1
	MARCO	ENST00000958830.1		c.19C>A	p.Leu7Ile	missense	Exon 1 of 17	ENSP00000628889.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Benign	0.87
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.20	T
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	1.5	L
PhyloP100		-0.12
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.66	N
REVEL	Benign	0.24
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.026	D
Polyphen		0.96	P
Vest4		0.20
MutPred		0.22		Gain of catalytic residue at L12 (P = 0.0391)
MVP		0.88
MPC		0.20
ClinPred		0.30	T
GERP RS		1.2
PromoterAI		-0.011	Neutral
Varity_R		0.086
gMVP		0.21
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

hg19: chr2-119699895;