20-35174936-A-T

Variant names:

• chr20-35174936-A-T
• rs376485381
• NM_006404.5:c.305A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006404.5(PROCR):​c.305A>T​(p.Gln102Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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. Q102R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 29)
• Consequence: PROCR NM_006404.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 0 publications found

Genes affected

PROCR (HGNC:9452): (protein C receptor) The protein encoded by this gene is a receptor for activated protein C, a serine protease activated by and involved in the blood coagulation pathway. The encoded protein is an N-glycosylated type I membrane protein that enhances the activation of protein C. Mutations in this gene have been associated with venous thromboembolism and myocardial infarction, as well as with late fetal loss during pregnancy. The encoded protein may also play a role in malarial infection and has been associated with cancer. [provided by RefSeq, Jul 2013]

MMP24-AS1-EDEM2 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12947264).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006404.5. 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
	PROCR	NM_006404.5	MANE Select	c.305A>T	p.Gln102Leu	missense	Exon 2 of 4	NP_006395.2
	MMP24-AS1-EDEM2	NM_001355008.2		c.-101-9065T>A		intron	N/A	NP_001341937.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PROCR	ENST00000216968.5	TSL:1 MANE Select	c.305A>T	p.Gln102Leu	missense	Exon 2 of 4	ENSP00000216968.3	Q9UNN8
	PROCR	ENST00000852804.1		c.305A>T	p.Gln102Leu	missense	Exon 3 of 5	ENSP00000522863.1
	PROCR	ENST00000852805.1		c.305A>T	p.Gln102Leu	missense	Exon 3 of 5	ENSP00000522864.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	2.4
DANN	Benign	0.93
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.091	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.053	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.8	L
PhyloP100		-1.7
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.18
Sift	Benign	0.20	T
Sift4G	Benign	0.23	T
Polyphen		0.017	B
Vest4		0.18
MutPred		0.47		Gain of methylation at R104 (P = 0.0691)
MVP		0.66
MPC		0.39
ClinPred		0.082	T
GERP RS		-2.6
PromoterAI		-0.28	Neutral
Varity_R		0.43
gMVP		0.37
Mutation Taster		=95/5	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: rs376485381; hg19: chr20-33762739;