1-171527810-A-G

Variant names:

• chr1-171527810-A-G
• rs1387686291
• NM_001387844.1:c.1220A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001387844.1(PRRC2C):​c.1220A>G​(p.His407Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRRC2C NM_001387844.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.26

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18873832).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2C	NM_001387844.1	c.1220A>G	p.His407Arg	missense_variant	Exon 11 of 35	ENST00000647382.2	NP_001374773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2C	ENST00000647382.2	c.1220A>G	p.His407Arg	missense_variant	Exon 11 of 35		NM_001387844.1	ENSP00000495867.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1429854 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 708514

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 17, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1214A>G (p.H405R) alteration is located in exon 11 (coding exon 10) of the PRRC2C gene. This alteration results from a A to G substitution at nucleotide position 1214, causing the histidine (H) at amino acid position 405 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	23
DANN	Benign	0.93
DEOGEN2	Benign	0.020	.;T;.;.
Eigen	Benign	0.0036
Eigen_PC	Benign	0.13
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.91	D;T;.;T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.7	.;.;L;L
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.4	.;N;N;N
REVEL	Benign	0.093
Sift	Benign	0.10	.;T;T;T
Sift4G	Benign	0.43	T;T;T;T
Polyphen		0.16, 0.39	.;B;B;B
Vest4		0.22, 0.27, 0.24
MutPred		0.23		.;Gain of solvent accessibility (P = 0.0514);.;.;
MVP		0.093
MPC		0.23
ClinPred		0.62	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.20

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: rs1387686291; hg19: chr1-171496949;