1-171515851-G-T

Variant names:

• chr1-171515851-G-T
• rs368030635
• NM_001387844.1:c.518G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001387844.1(PRRC2C):​c.518G>T​(p.Arg173Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000694 in 1,441,674 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R173H) has been classified as Uncertain significance.

• 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: 9.52

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2C	NM_001387844.1	c.518G>T	p.Arg173Leu	missense_variant	Exon 5 of 35	ENST00000647382.2	NP_001374773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2C	ENST00000647382.2	c.518G>T	p.Arg173Leu	missense_variant	Exon 5 of 35		NM_001387844.1	ENSP00000495867.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000425 AC: 1 AN: 235232 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 127608

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000919

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441674 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 717244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.10	T;.;.
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	1.0	D;.;D
M_CAP	Benign	0.0071	T
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.8	.;M;M
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.1	D;D;D
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.80
MutPred		0.20		.;Loss of methylation at R171 (P = 0.052);Loss of methylation at R171 (P = 0.052);
MVP		0.40
MPC		0.23
ClinPred		0.94	D
GERP RS		5.6
gMVP		0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs368030635; hg19: chr1-171484990;