Genetic Variant MRC1:p.Thr399Ser (chr10-17849710-A-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_002438.4(MRC1):c.1195A>T(p.Thr399Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000384 in 780,518 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: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

MRC1
NM_002438.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.38

Publications

10 publications found

Variant links:

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]

MRC1 links:

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ACMG classification

Classification was made for transcript

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=0.31254944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRC1	NM_002438.4 link	c.1195A>T	p.Thr399Ser	missense_variant	Exon 7 of 30	ENST00000569591.3	NP_002429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRC1	ENST00000569591.3 link	c.1195A>T	p.Thr399Ser	missense_variant	Exon 7 of 30	1	NM_002438.4	ENSP00000455897.1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151780

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000318

AC:

AN:

628738

Hom.:

Cov.:

AF XY:

0.00000584

AC XY:

AN XY:

342520

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

17688

American (AMR)

AF:

0.00

AC:

AN:

43740

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20980

East Asian (EAS)

AF:

0.00

AC:

AN:

36064

South Asian (SAS)

AF:

0.0000143

AC:

AN:

69798

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4148

European-Non Finnish (NFE)

AF:

0.00000286

AC:

AN:

350078

Other (OTH)

AF:

0.00

AC:

AN:

33098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151780

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74106

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41308

American (AMR)

AF:

0.00

AC:

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67958

Other (OTH)

AF:

0.00

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

5628

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.096

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.58

M_CAP

Benign

0.0095

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.61

PhyloP100

4.4

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.18

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.011

Polyphen

0.015

Vest4

0.20

MutPred

0.72

Gain of disorder (P = 0.0389);

MVP

0.20

ClinPred

0.63

GERP RS

3.5

Varity_R

0.26

gMVP

0.47

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over