2-118970242-G-T

Variant names:

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

Variant summary

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

The NM_006770.4(MARCO):​c.328G>T​(p.Ala110Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,832 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MARCO NM_006770.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=0.084995925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARCO	NM_006770.4	c.328G>T	p.Ala110Ser	missense_variant	Exon 3 of 17	ENST00000327097.5	NP_006761.1
MARCO	XM_011512082.3	c.328G>T	p.Ala110Ser	missense_variant	Exon 3 of 17		XP_011510384.1
MARCO	XM_017005171.3	c.328G>T	p.Ala110Ser	missense_variant	Exon 3 of 9		XP_016860660.1
MARCO	XM_011512083.4	c.98-4091G>T		intron_variant	Intron 1 of 13		XP_011510385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARCO	ENST00000327097.5	c.328G>T	p.Ala110Ser	missense_variant	Exon 3 of 17	1	NM_006770.4	ENSP00000318916.4
MARCO	ENST00000412481.1	c.94G>T	p.Ala32Ser	missense_variant	Exon 4 of 4	4		ENSP00000409192.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461832 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.039
DANN	Benign	0.63
DEOGEN2	Benign	0.051	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.038	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-0.56	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.020	N;N
REVEL	Benign	0.13
Sift	Benign	0.74	T;T
Sift4G	Benign	0.68	T;T
Polyphen		0.14	B;.
Vest4		0.22
MutPred		0.30		Gain of disorder (P = 0.0315);.;
MVP		0.33
MPC		0.29
ClinPred		0.083	T
GERP RS		-7.8
Varity_R		0.035
gMVP		0.31

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

Other links and lift over

dbSNP: rs1456356736; hg19: chr2-119727818;