1-171522198-A-T

Variant names:

• chr1-171522198-A-T
• NM_001387844.1:c.772A>T

Variant summary

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

The NM_001387844.1(PRRC2C):​c.772A>T​(p.Met258Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000139 in 1,437,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PRRC2C NM_001387844.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.62

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=0.09548798).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRC2C	NM_001387844.1	c.772A>T	p.Met258Leu	missense_variant	Exon 7 of 35	ENST00000647382.2	NP_001374773.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRC2C	ENST00000647382.2	c.772A>T	p.Met258Leu	missense_variant	Exon 7 of 35		NM_001387844.1	ENSP00000495867.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1437054 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 715418

Gnomad4 AFR exome AF: 0.0000604

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

Sep 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.766A>T (p.M256L) alteration is located in exon 7 (coding exon 6) of the PRRC2C gene. This alteration results from a A to T substitution at nucleotide position 766, causing the methionine (M) at amino acid position 256 to be replaced by a leucine (L). 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	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.87
DEOGEN2	Benign	0.0055	.;T;.;.
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;T;.;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.095	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.1	.;.;L;L
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-0.10	.;N;N;N
REVEL	Benign	0.15
Sift	Benign	0.66	.;T;T;T
Sift4G	Benign	0.67	T;T;T;T
Polyphen		0.0, 0.0010	.;B;B;B
Vest4		0.41, 0.43
MutPred		0.21		.;Gain of catalytic residue at M258 (P = 0.0904);.;.;
MVP		0.19
MPC		0.17
ClinPred		0.81	D
GERP RS		4.7
gMVP		0.30

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-171491337;