Genetic Variant NM_006813.3:c.307C>T (chr6-89081201-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_006813.3(PNRC1):c.307C>T(p.Arg103Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000778 in 1,413,412 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

PNRC1
NM_006813.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.422

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.759

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.307C>T	p.Arg103Trp	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.307C>T	p.Arg103Trp	missense	Exon 1 of 2	ENSP00000336931.3	Q12796-1
	PNRC1	ENST00000369472.1	TSL:2	c.-16+228C>T		intron	N/A	ENSP00000358484.1	Q49A59

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000298

AC:

AN:

167978

AF XY:

0.0000427

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000111

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000274

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000778

AC:

AN:

1413412

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

701018

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32490

American (AMR)

AF:

0.0000516

AC:

AN:

38760

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25452

East Asian (EAS)

AF:

0.00

AC:

AN:

37256

South Asian (SAS)

AF:

0.0000363

AC:

AN:

82656

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36172

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5612

European-Non Finnish (NFE)

AF:

0.00000547

AC:

AN:

1096022

Other (OTH)

AF:

0.00

AC:

AN:

58992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

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

Pathogenic

0.77

BayesDel_addAF

Benign

-0.0037

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

Eigen

Benign

-0.080

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.76

M_CAP

Pathogenic

0.87

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.1

PhyloP100

0.42

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-1.6

REVEL

Benign

0.23

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.56

MutPred

0.32

Gain of catalytic residue at P106 (P = 0.0244)

MVP

0.13

MPC

1.5

ClinPred

0.69

GERP RS

1.1

PromoterAI

0.040

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.28

gMVP

0.27

Mutation Taster

=89/11

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over