1-171513097-A-C

Variant names:

• chr1-171513097-A-C
• rs371016782
• NM_001387844.1:c.215A>C

Variant summary

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

The NM_001387844.1(PRRC2C):​c.215A>C​(p.Asn72Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,526 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. N72S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRRC2C NM_001387844.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.95
• 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.215A>C	p.Asn72Thr	missense	Exon 3 of 35	NP_001374773.1	Q9Y520-7
	PRRC2C	NM_015172.4		c.209A>C	p.Asn70Thr	missense	Exon 3 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.215A>C	p.Asn72Thr	missense	Exon 3 of 35	ENSP00000495867.2	Q9Y520-7
	PRRC2C	ENST00000426496.6	TSL:1	c.209A>C	p.Asn70Thr	missense	Exon 2 of 33	ENSP00000410219.3	Q9Y520-4
	PRRC2C	ENST00000367742.7	TSL:5	c.215A>C	p.Asn72Thr	missense	Exon 3 of 34	ENSP00000356716.3	E7EPN9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461526 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727016

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111774

Other (OTH) AF: 0.0000166 AC: 1 AN: 60366

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	25
DANN	Benign	0.96
DEOGEN2	Benign	0.043	T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.83
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		8.9
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0080	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.67
MutPred		0.54		Gain of phosphorylation at N70 (P = 0.0405)
MVP		0.22
MPC		0.19
ClinPred		0.92	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.56
Mutation Taster		=47/53	disease causing

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: rs371016782; hg19: chr1-171482236;