Genetic Variant PNRC1:p.Thr321Thr (chr6-89084175-G-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0450

Publications

18 publications found

Variant links:

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]

PNRC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 link	c.963G>C	p.Thr321Thr	synonymous_variant	Exon 2 of 2	ENST00000336032.4	NP_006804.1	Q12796-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PNRC1	ENST00000336032.4 link	c.963G>C	p.Thr321Thr	synonymous_variant	Exon 2 of 2	1	NM_006813.3	ENSP00000336931.3	Q12796-1
PNRC1	ENST00000354922.3 link	c.408G>C	p.Thr136Thr	synonymous_variant	Exon 2 of 2	1		ENSP00000347000.3	Q49A59
PNRC1	ENST00000369472.1 link	c.408G>C	p.Thr136Thr	synonymous_variant	Exon 2 of 2	2		ENSP00000358484.1	Q49A59

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33397

AN:

151870

Hom.:

4475

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.253

AC:

57078

AN:

225586

AF XY:

0.246

show subpopulations

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 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.:

AF XY:

0.196

AC XY:

139048

AN XY:

707742

show subpopulations

African (AFR)

AF:

0.217

AC:

6840

AN:

31454

American (AMR)

AF:

0.366

AC:

13041

AN:

35634

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

4286

AN:

24464

East Asian (EAS)

AF:

0.666

AC:

26208

AN:

39332

South Asian (SAS)

AF:

0.292

AC:

23537

AN:

80472

European-Finnish (FIN)

AF:

0.245

AC:

12967

AN:

52840

Middle Eastern (MID)

AF:

0.150

AC:

839

AN:

5598

European-Non Finnish (NFE)

AF:

0.163

AC:

178788

AN:

1098346

Other (OTH)

AF:

0.212

AC:

12457

AN:

58840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

9961

19922

29882

39843

49804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6934

13868

20802

27736

34670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.220

AC:

33416

AN:

151988

Hom.:

4479

Cov.:

AF XY:

0.232

AC XY:

17196

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.221

AC:

9177

AN:

41458

American (AMR)

AF:

0.301

AC:

4591

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

641

AN:

3470

East Asian (EAS)

AF:

0.680

AC:

3508

AN:

5158

South Asian (SAS)

AF:

0.310

AC:

1497

AN:

4824

European-Finnish (FIN)

AF:

0.252

AC:

2654

AN:

10534

Middle Eastern (MID)

AF:

0.154

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.159

AC:

10778

AN:

67964

Other (OTH)

AF:

0.190

AC:

402

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1239

2479

3718

4958

6197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.67

PhyloP100

-0.045

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over