chr1-171517702-A-G

Variant names:

• chr1-171517702-A-G
• rs758869112
• NM_001387844.1:c.638A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001387844.1(PRRC2C):​c.638A>G​(p.Asn213Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PRRC2C NM_001387844.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.752
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.023919374).

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.638A>G	p.Asn213Ser	missense	Exon 6 of 35	NP_001374773.1	Q9Y520-7
	PRRC2C	NM_015172.4		c.632A>G	p.Asn211Ser	missense	Exon 6 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.638A>G	p.Asn213Ser	missense	Exon 6 of 35	ENSP00000495867.2	Q9Y520-7
	PRRC2C	ENST00000426496.6	TSL:1	c.632A>G	p.Asn211Ser	missense	Exon 5 of 33	ENSP00000410219.3	Q9Y520-4
	PRRC2C	ENST00000367742.7	TSL:5	c.638A>G	p.Asn213Ser	missense	Exon 6 of 34	ENSP00000356716.3	E7EPN9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250686 AF XY: 0.00000738

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461698 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727128

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111868

Other (OTH) AF: 0.00 AC: 0 AN: 60374

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

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	Benign	0.063
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	13
DANN	Benign	0.88
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.024	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.28	N
PhyloP100		0.75
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.060
Sift	Benign	0.93	T
Sift4G	Benign	0.65	T
Polyphen		0.0	B
Vest4		0.056
MutPred		0.11		Gain of phosphorylation at N213 (P = 0.0546)
MVP		0.043
MPC		0.15
ClinPred		0.038	T
GERP RS		0.40
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.6
gMVP		0.11
Mutation Taster		=88/12	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: rs758869112; hg19: chr1-171486841;