NM_006770.4:c.328G>A

Variant names:

• chr2-118970242-G-A
• rs1456356736
• NM_006770.4:c.328G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006770.4(MARCO):​c.328G>A​(p.Ala110Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A110E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: MARCO NM_006770.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.10
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06610492).

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.328G>A	p.Ala110Thr	missense	Exon 3 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.328G>A	p.Ala110Thr	missense	Exon 3 of 17	ENSP00000318916.4	Q9UEW3-1
	MARCO	ENST00000874357.1		c.328G>A	p.Ala110Thr	missense	Exon 3 of 18	ENSP00000544416.1
	MARCO	ENST00000958830.1		c.328G>A	p.Ala110Thr	missense	Exon 3 of 17	ENSP00000628889.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461832 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.098
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	0.11
DANN	Benign	0.67
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Benign	0.43	N
PhyloP100		-1.1
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.15
Sift	Benign	0.69	T
Sift4G	Benign	0.66	T
Polyphen		0.0020	B
Vest4		0.11
MutPred		0.21		Loss of MoRF binding (P = 0.1293)
MVP		0.32
MPC		0.31
ClinPred		0.074	T
GERP RS		-7.8
Varity_R		0.021
gMVP		0.34
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs1456356736; hg19: chr2-119727818;