rs376485381

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-35174936-A-G
• chr20-35174936-A-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006404.5(PROCR):​c.305A>G​(p.Gln102Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000649 in 1,232,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000065 (0 hom.)
• Consequence: PROCR NM_006404.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061030716).
• BP6: Variant 20-35174936-A-G is Benign according to our data. Variant chr20-35174936-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3310279.Status of the report is criteria_provided_single_submitter, 1 stars.

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>G	p.Gln102Arg	missense	Exon 2 of 4	NP_006395.2
	MMP24-AS1-EDEM2	NM_001355008.2		c.-101-9065T>C		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>G	p.Gln102Arg	missense	Exon 2 of 4	ENSP00000216968.3	Q9UNN8
	PROCR	ENST00000852804.1		c.305A>G	p.Gln102Arg	missense	Exon 3 of 5	ENSP00000522863.1
	PROCR	ENST00000852805.1		c.305A>G	p.Gln102Arg	missense	Exon 3 of 5	ENSP00000522864.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000649 AC: 8 AN: 1232116 Hom.: 0 Cov.: 46 AF XY: 0.00 AC XY: 0 AN XY: 607764

African (AFR) AF: 0.00 AC: 0 AN: 27208

American (AMR) AF: 0.00 AC: 0 AN: 33618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17788

East Asian (EAS) AF: 0.00 AC: 0 AN: 20400

South Asian (SAS) AF: 0.00 AC: 0 AN: 81262

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4560

European-Non Finnish (NFE) AF: 0.00000516 AC: 5 AN: 968270

Other (OTH) AF: 0.0000653 AC: 3 AN: 45922

GnomAD4 genome Cov.: 29

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.21
DANN	Benign	0.79
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.67	N
PhyloP100		-1.7
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.12
Sift	Benign	0.63	T
Sift4G	Benign	0.94	T
Polyphen		0.0	B
Vest4		0.064
MutPred		0.47		Gain of MoRF binding (P = 0.0657)
MVP		0.50
MPC		0.43
ClinPred		0.032	T
GERP RS		-2.6
PromoterAI		0.096	Neutral
Varity_R		0.29
gMVP		0.17
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: rs376485381; hg19: chr20-33762739;