chr1-171515821-A-T

Variant names:

• chr1-171515821-A-T
• NM_001387844.1:c.488A>T

Variant summary

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

The NM_001387844.1(PRRC2C):​c.488A>T​(p.Asp163Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,274 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. D163G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRRC2C NM_001387844.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.87

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.488A>T	p.Asp163Val	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.488A>T	p.Asp163Val	missense_variant	Exon 5 of 35		NM_001387844.1	ENSP00000495867.2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459928 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726266

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000656 AC: 1 AN: 152346 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74498

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.036	T;.;.
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;.;D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.46	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	.;L;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.6	D;D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0080	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.63
MutPred		0.51		.;Loss of glycosylation at K157 (P = 0.1524);Loss of glycosylation at K157 (P = 0.1524);
MVP		0.10
MPC		0.27
ClinPred		0.96	D
GERP RS		5.6
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-171484960;