20-35174893-T-C

Variant names:

• chr20-35174893-T-C
• rs150846093
• NM_006404.5:c.262T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_006404.5(PROCR):​c.262T>C​(p.Ser88Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000979 in 1,609,320 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (2 hom., cov: 29)
  • Exomes 𝑓: 0.00097 (16 hom.)
• Consequence: PROCR NM_006404.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.93
• Publications: 7 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010937989).
• BP6: Variant 20-35174893-T-C is Benign according to our data. Variant chr20-35174893-T-C is described in ClinVar as Benign. ClinVar VariationId is 731572.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.262T>C	p.Ser88Pro	missense	Exon 2 of 4	NP_006395.2
	MMP24-AS1-EDEM2	NM_001355008.2		c.-101-9022A>G		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.262T>C	p.Ser88Pro	missense	Exon 2 of 4	ENSP00000216968.3	Q9UNN8
	PROCR	ENST00000852804.1		c.262T>C	p.Ser88Pro	missense	Exon 3 of 5	ENSP00000522863.1
	PROCR	ENST00000852805.1		c.262T>C	p.Ser88Pro	missense	Exon 3 of 5	ENSP00000522864.1

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 164 AN: 151332 Hom.: 2 Cov.: 29

Gnomad AFR AF: 0.000146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000395

Gnomad ASJ AF: 0.0350

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00241

GnomAD2 exomes AF: 0.00186 AC: 444 AN: 238974 AF XY: 0.00188

Gnomad AFR exome AF: 0.0000649

Gnomad AMR exome AF: 0.000540

Gnomad ASJ exome AF: 0.0370

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000431

Gnomad OTH exome AF: 0.00291

GnomAD4 exome AF: 0.000968 AC: 1412 AN: 1457988 Hom.: 16 Cov.: 46 AF XY: 0.00106 AC XY: 765 AN XY: 725096

African (AFR) AF: 0.0000598 AC: 2 AN: 33426

American (AMR) AF: 0.000546 AC: 24 AN: 43952

Ashkenazi Jewish (ASJ) AF: 0.0371 AC: 964 AN: 25956

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39596

South Asian (SAS) AF: 0.00 AC: 0 AN: 85916

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 52880

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5760

European-Non Finnish (NFE) AF: 0.000236 AC: 262 AN: 1110302

Other (OTH) AF: 0.00259 AC: 156 AN: 60200

GnomAD4 genome AF: 0.00108 AC: 164 AN: 151332 Hom.: 2 Cov.: 29 AF XY: 0.00118 AC XY: 87 AN XY: 73848

African (AFR) AF: 0.000146 AC: 6 AN: 41120

American (AMR) AF: 0.000395 AC: 6 AN: 15194

Ashkenazi Jewish (ASJ) AF: 0.0350 AC: 121 AN: 3460

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5118

South Asian (SAS) AF: 0.00 AC: 0 AN: 4800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 67902

Other (OTH) AF: 0.00241 AC: 5 AN: 2078

Alfa AF: 0.00176 Hom.: 7

Bravo AF: 0.00128

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.00128 AC: 155

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.65
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	0.049
DANN	Benign	0.30
DEOGEN2	Benign	0.31	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.5
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.011	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.69	N
PhyloP100		-2.9
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N
REVEL	Uncertain	0.29
Sift	Benign	0.28	T
Sift4G	Benign	0.28	T
Polyphen		0.078	B
Vest4		0.24
MVP		0.41
MPC		0.56
ClinPred		0.014	T
GERP RS		-10
PromoterAI		-0.022	Neutral
Varity_R		0.46
gMVP		0.62
Mutation Taster		=96/4	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: rs150846093; hg19: chr20-33762696;