10-17849710-A-C

Variant names:

• chr10-17849710-A-C
• rs71497223
• NM_002438.4:c.1195A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002438.4(MRC1):​c.1195A>C​(p.Thr399Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000159 in 628,738 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: MRC1 NM_002438.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38
• Publications: 0 publications found

Genes affected

MRC1 (HGNC:7228): (mannose receptor C-type 1) The recognition of complex carbohydrate structures on glycoproteins is an important part of several biological processes, including cell-cell recognition, serum glycoprotein turnover, and neutralization of pathogens. The protein encoded by this gene is a type I membrane receptor that mediates the endocytosis of glycoproteins by macrophages. The protein has been shown to bind high-mannose structures on the surface of potentially pathogenic viruses, bacteria, and fungi so that they can be neutralized by phagocytic engulfment.[provided by RefSeq, Sep 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35581955).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002438.4. 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
	MRC1	NM_002438.4	MANE Select	c.1195A>C	p.Thr399Pro	missense	Exon 7 of 30	NP_002429.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRC1	ENST00000569591.3	TSL:1 MANE Select	c.1195A>C	p.Thr399Pro	missense	Exon 7 of 30	ENSP00000455897.1
	MRC1	ENST00000954013.1		c.1081A>C	p.Thr361Pro	missense	Exon 6 of 29	ENSP00000624072.1
	MRC1	ENST00000884128.1		c.1021A>C	p.Thr341Pro	missense	Exon 6 of 29	ENSP00000554187.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000159 AC: 1 AN: 628738 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 342520

African (AFR) AF: 0.00 AC: 0 AN: 17688

American (AMR) AF: 0.00 AC: 0 AN: 43740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20980

East Asian (EAS) AF: 0.00 AC: 0 AN: 36064

South Asian (SAS) AF: 0.00 AC: 0 AN: 69798

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4148

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 350078

Other (OTH) AF: 0.00 AC: 0 AN: 33098

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.58	N
PhyloP100		4.4
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.6	N
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.016	D
Polyphen		0.14	B
Vest4		0.23
MutPred		0.69		Loss of phosphorylation at T399 (P = 0.0462)
MVP		0.14
ClinPred		0.65	D
GERP RS		3.5
Varity_R		0.66
gMVP		0.80
Mutation Taster		=97/3	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

dbSNP: rs71497223; hg19: chr10-18138639;