NM_002438.4:c.1195A>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T399A) has been classified as Likely benign.

• 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

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

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=0.35581955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRC1	NM_002438.4	c.1195A>C	p.Thr399Pro	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	c.1195A>C	p.Thr399Pro	missense_variant	Exon 7 of 30	1	NM_002438.4	ENSP00000455897.1

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

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: 0.0000188

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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
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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-18138639;