NM_001387844.1:c.883C>T

Variant names:

• chr1-171523270-C-T
• rs1673952220
• NM_001387844.1:c.883C>T

Variant summary

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

The NM_001387844.1(PRRC2C):​c.883C>T​(p.Arg295Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,156 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRRC2C NM_001387844.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.39
• Publications: 0 publications found

Genes affected

PRRC2C (HGNC:24903): (proline rich coiled-coil 2C) Enables protein C-terminus binding activity. Involved in stress granule assembly. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387844.1. 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
	PRRC2C	NM_001387844.1	MANE Select	c.883C>T	p.Arg295Cys	missense	Exon 8 of 35	NP_001374773.1	Q9Y520-7
	PRRC2C	NM_015172.4		c.877C>T	p.Arg293Cys	missense	Exon 8 of 34	NP_055987.2	Q9Y520-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRC2C	ENST00000647382.2	MANE Select	c.883C>T	p.Arg295Cys	missense	Exon 8 of 35	ENSP00000495867.2	Q9Y520-7
	PRRC2C	ENST00000426496.6	TSL:1	c.877C>T	p.Arg293Cys	missense	Exon 7 of 33	ENSP00000410219.3	Q9Y520-4
	PRRC2C	ENST00000367742.7	TSL:5	c.883C>T	p.Arg295Cys	missense	Exon 8 of 34	ENSP00000356716.3	E7EPN9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461156 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726838

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111542

Other (OTH) AF: 0.00 AC: 0 AN: 60362

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00666416), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.096	T
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.4
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-6.6	D
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.016	D
Polyphen		1.0	D
Vest4		0.77
MVP		0.21
MPC		0.25
ClinPred		1.0	D
GERP RS		5.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.65
Mutation Taster		=60/40	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1673952220; hg19: chr1-171492409;