Genetic Variant PROCR:p.Ser219Gly (chr20-35176751-AGT-GGC) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is The variant received 2 classification points (ACMG Germline Pathogenicity v2019). PM2

The NM_006404.5(PROCR):c.655_657delAGTinsGGC (p.Ser219Gly) variant causes a missense change. Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. This exact variant is curated in the UniProt human variants database as Uncertain Significance.

Frequency

Genomes: not found (cov: 32)

Consequence

PROCR
NM_006404.5 missense

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.515

Publications

0 publications found

Variant links:

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]

PROCR links:

MMP24-AS1-EDEM2 (HGNC:):

MMP24-AS1-EDEM2 links:

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new If you want to explore the variant's impact on the transcript NM_006404.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Show applied only (1)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	PM2Absent/extremely low in population databases		Absent from gnomAD (AR/unknown gene) — PM2; Absent from gnomAD at well-covered site (MOI: unknown) (threshold 0.001) — PM2 moderate.

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_006404.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	PROCR NM_006404.5	MANE Select	c.655_657delAGTinsGGC p.Ser219Gly	missense	N/A	Prot: NP_006395.2
	MMP24-AS1-EDEM2 NM_001355008.2		c.-101-10882_-101-10880delACTinsGCC	intron	Intron 4 of 14	Prot: NP_001341937.1

PROCR NM_006404.5

MANE Select

HGVSc / HGVSpc.655_657delAGTinsGGCp.Ser219Gly

Exon rankN/A

missense

Prot: NP_006395.2

MMP24-AS1-EDEM2 NM_001355008.2

HGVSc / HGVSpc.-101-10882_-101-10880delACTinsGCC

Exon rankIntron 4 of 14

intron

Prot: NP_001341937.1

Ensembl Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
PROCR ENST00000216968.5	TSL:1MANE Select	c.655_657delAGTinsGGC p.Ser219Gly	missense	N/A	Prot: ENSP00000216968.3 UniProt: Q9UNN8
PROCR ENST00000852804.1		c.655_657delAGTinsGGC p.Ser219Gly	missense	N/A	Prot: ENSP00000522863.1 UniProt: Q9UNN8
PROCR ENST00000852805.1		c.655_657delAGTinsGGC p.Ser219Gly	missense	N/A	Prot: ENSP00000522864.1 UniProt: Q9UNN8

PROCR ENST00000216968.5

TSL:1MANE Select

HGVSc / HGVSpc.655_657delAGTinsGGCp.Ser219Gly

Exon rankN/A

missense

Prot: ENSP00000216968.3UniProt: Q9UNN8

PROCR ENST00000852804.1

HGVSc / HGVSpc.655_657delAGTinsGGCp.Ser219Gly

Exon rankN/A

missense

Prot: ENSP00000522863.1UniProt: Q9UNN8

PROCR ENST00000852805.1

HGVSc / HGVSpc.655_657delAGTinsGGCp.Ser219Gly

Exon rankN/A

missense

Prot: ENSP00000522864.1UniProt: Q9UNN8

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:32
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:32

Showing 2 sources

Tested, but no data found:GnomAD4 exomeIf GnomAD4 is missing, the position is probably not covered by the project.

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Benign	0.52

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence