2-118974364-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006770.4(MARCO):​c.492G>A​(p.Met164Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000055 in 1,454,648 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

MARCO
NM_006770.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.22
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.049111307).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MARCONM_006770.4 linkuse as main transcriptc.492G>A p.Met164Ile missense_variant 5/17 ENST00000327097.5
MARCOXM_011512082.3 linkuse as main transcriptc.492G>A p.Met164Ile missense_variant 5/17
MARCOXM_011512083.4 linkuse as main transcriptc.129G>A p.Met43Ile missense_variant 2/14
MARCOXM_017005171.3 linkuse as main transcriptc.492G>A p.Met164Ile missense_variant 5/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MARCOENST00000327097.5 linkuse as main transcriptc.492G>A p.Met164Ile missense_variant 5/171 NM_006770.4 P1Q9UEW3-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000550
AC:
8
AN:
1454648
Hom.:
0
Cov.:
32
AF XY:
0.00000692
AC XY:
5
AN XY:
722828
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00000631
Gnomad4 OTH exome
AF:
0.0000167
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378

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 submitterclinical testingAmbry GeneticsDec 16, 2022The c.492G>A (p.M164I) alteration is located in exon 5 (coding exon 5) of the MARCO gene. This alteration results from a G to A substitution at nucleotide position 492, causing the methionine (M) at amino acid position 164 to be replaced by an isoleucine (I). 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
0.19
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
0.068
DANN
Benign
0.45
DEOGEN2
Benign
0.21
T
Eigen
Benign
-1.7
Eigen_PC
Benign
-1.9
FATHMM_MKL
Benign
0.037
N
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.0099
T
MetaRNN
Benign
0.049
T
MetaSVM
Benign
-0.29
T
MutationAssessor
Benign
0.27
N
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.33
N
REVEL
Benign
0.13
Sift
Benign
0.28
T
Sift4G
Benign
0.20
T
Polyphen
0.036
B
Vest4
0.16
MutPred
0.35
Gain of ubiquitination at K159 (P = 0.1051);
MVP
0.24
MPC
0.063
ClinPred
0.71
D
GERP RS
-7.9
Varity_R
0.085
gMVP
0.14

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1185170201; hg19: chr2-119731940; API