dbSNP rs144080988: MARCO:p.Leu68Met (chr2-118970116-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006770.4(MARCO):c.202C>A(p.Leu68Met) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

MARCO
NM_006770.4 missense, splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.465

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29138952).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCO	NM_006770.4 link	c.202C>A	p.Leu68Met	missense_variant, splice_region_variant	Exon 3 of 17	ENST00000327097.5	NP_006761.1	Q9UEW3-1Q4ZG40
MARCO	XM_011512082.3 link	c.202C>A	p.Leu68Met	missense_variant, splice_region_variant	Exon 3 of 17		XP_011510384.1	Q9UEW3-1Q4ZG40
MARCO	XM_017005171.3 link	c.202C>A	p.Leu68Met	missense_variant, splice_region_variant	Exon 3 of 9		XP_016860660.1
MARCO	XM_011512083.4 link	c.98-4217C>A		intron_variant	Intron 1 of 13		XP_011510385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MARCO	ENST00000327097.5 link	c.202C>A	p.Leu68Met	missense_variant, splice_region_variant	Exon 3 of 17	1	NM_006770.4	ENSP00000318916.4	Q9UEW3-1
MARCO	ENST00000412481 link	c.-33C>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 4 of 4	4		ENSP00000409192.1	C9JKT8
MARCO	ENST00000412481.1 link	c.-33C>A		splice_region_variant	Exon 4 of 4	4		ENSP00000409192.1	C9JKT8
MARCO	ENST00000412481 link	c.-33C>A		5_prime_UTR_variant	Exon 4 of 4	4		ENSP00000409192.1	C9JKT8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250168

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135486

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461474

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727060

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.11

Eigen

Benign

-0.091

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.46

M_CAP

Uncertain

0.086

MetaRNN

Benign

0.29

MetaSVM

Uncertain

-0.12

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.71

REVEL

Uncertain

0.30

Sift

Benign

0.041

Sift4G

Uncertain

0.020

Polyphen

0.92

Vest4

0.29

MutPred

0.44

Gain of catalytic residue at V64 (P = 0.1567);

MVP

0.89

MPC

0.31

ClinPred

0.61

GERP RS

3.5

Varity_R

0.14

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over