Genetic Variant NM_006813.3:c.161C>G (chr6-89081055-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006813.3(PNRC1):c.161C>G(p.Thr54Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000355 in 1,610,580 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 1 hom. )

Consequence

PNRC1
NM_006813.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.437

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019788116).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006813.3. 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
	PNRC1	NM_006813.3	MANE Select	c.161C>G	p.Thr54Ser	missense	Exon 1 of 2	NP_006804.1	Q12796-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNRC1	ENST00000336032.4	TSL:1 MANE Select	c.161C>G	p.Thr54Ser	missense	Exon 1 of 2	ENSP00000336931.3	Q12796-1
	PNRC1	ENST00000369472.1	TSL:2	c.-16+82C>G		intron	N/A	ENSP00000358484.1	Q49A59

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

152238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000723

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000471

AC:

116

AN:

246540

AF XY:

0.000470

show subpopulations

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:

0.000105

Gnomad NFE exome

AF:

0.000988

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.000367

AC:

535

AN:

1458342

Hom.:

Cov.:

AF XY:

0.000333

AC XY:

242

AN XY:

725696

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39682

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.000378

AC:

AN:

50268

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000443

AC:

492

AN:

1111702

Other (OTH)

AF:

0.000381

AC:

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

131

164

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000243

AC:

AN:

152238

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41476

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000382

AC:

AN:

68052

Other (OTH)

AF:

0.000956

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000201

Hom.:

Bravo

AF:

0.000261

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000816

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000474

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.065

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.48

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

0.44

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.58

REVEL

Benign

0.077

Sift

Benign

0.085

Sift4G

Benign

0.22

Polyphen

0.094

Vest4

0.13

MutPred

0.14

Gain of relative solvent accessibility (P = 0.0082)

MVP

0.15

MPC

1.0

ClinPred

0.12

GERP RS

3.9

PromoterAI

0.022

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.14

gMVP

0.12

Mutation Taster

=95/5

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over