NM_006813.3:c.963G>C

Variant names:

• chr6-89084175-G-C
• rs1130809
• NM_006813.3:c.963G>C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006813.3(PNRC1):​c.963G>C​(p.Thr321Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 1,578,968 control chromosomes in the GnomAD database, including 38,419 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4479 hom., cov: 33)
  • Exomes 𝑓: 0.20 (33940 hom.)
• Consequence: PNRC1 NM_006813.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0450

Genes affected

PNRC1 (HGNC:17278): (proline rich nuclear receptor coactivator 1) Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.045 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNRC1	NM_006813.3	c.963G>C	p.Thr321Thr	synonymous_variant	Exon 2 of 2	ENST00000336032.4	NP_006804.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNRC1	ENST00000336032.4	c.963G>C	p.Thr321Thr	synonymous_variant	Exon 2 of 2	1	NM_006813.3	ENSP00000336931.3
PNRC1	ENST00000354922.3	c.408G>C	p.Thr136Thr	synonymous_variant	Exon 2 of 2	1		ENSP00000347000.3
PNRC1	ENST00000369472.1	c.408G>C	p.Thr136Thr	synonymous_variant	Exon 2 of 2	2		ENSP00000358484.1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33397 AN: 151870 Hom.: 4475 Cov.: 33

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.135

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.192

GnomAD3 exomes AF: 0.253 AC: 57078 AN: 225586 Hom.: 9643 AF XY: 0.246 AC XY: 30019 AN XY: 122246

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.378

Gnomad ASJ exome AF: 0.175

Gnomad EAS exome AF: 0.683

Gnomad SAS exome AF: 0.295

Gnomad FIN exome AF: 0.250

Gnomad NFE exome AF: 0.157

Gnomad OTH exome AF: 0.223

GnomAD4 exome AF: 0.195 AC: 278963 AN: 1426980 Hom.: 33940 Cov.: 31 AF XY: 0.196 AC XY: 139048 AN XY: 707742

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.366

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.666

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.212

GnomAD4 genome AF: 0.220 AC: 33416 AN: 151988 Hom.: 4479 Cov.: 33 AF XY: 0.232 AC XY: 17196 AN XY: 74274

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.190

Alfa AF: 0.172 Hom.: 793

Bravo AF: 0.226

Asia WGS AF: 0.426 AC: 1483 AN: 3478

EpiCase AF: 0.156

EpiControl AF: 0.158

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.0
DANN	Benign	0.67

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: rs1130809; hg19: chr6-89793894; COSMIC: COSV60138890; COSMIC: COSV60138890;