1-171532497-A-T

Variant names:

• chr1-171532497-A-T
• rs704839
• NM_001387844.1:c.1409A>T

Variant summary

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

The NM_001387844.1(PRRC2C):​c.1409A>T​(p.Glu470Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,094 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: PRRC2C NM_001387844.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.11
• Publications: 2 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRC2C	NM_001387844.1	MANE Select	c.1409A>T	p.Glu470Val	missense	Exon 12 of 35	NP_001374773.1
	PRRC2C	NM_015172.4		c.1403A>T	p.Glu468Val	missense	Exon 12 of 34	NP_055987.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRC2C	ENST00000647382.2	MANE Select	c.1409A>T	p.Glu470Val	missense	Exon 12 of 35	ENSP00000495867.2
	PRRC2C	ENST00000426496.6	TSL:1	c.1403A>T	p.Glu468Val	missense	Exon 11 of 33	ENSP00000410219.3
	PRRC2C	ENST00000367742.7	TSL:5	c.1409A>T	p.Glu470Val	missense	Exon 12 of 34	ENSP00000356716.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000407 AC: 1 AN: 245620 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459094 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 725498

African (AFR) AF: 0.00 AC: 0 AN: 33432

American (AMR) AF: 0.00 AC: 0 AN: 44254

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26058

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 85590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53314

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110722

Other (OTH) AF: 0.00 AC: 0 AN: 60312

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Benign	0.95
DEOGEN2	Benign	0.095	T
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		9.1
PrimateAI	Uncertain	0.67	T
PROVEAN	Pathogenic	-6.4	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.29		Loss of helix (P = 0.0017)
MVP		0.15
MPC		0.22
ClinPred		0.94	D
GERP RS		6.0
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		3.7
gMVP		0.38
Mutation Taster		=57/43	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: rs704839; hg19: chr1-171501636;