Genetic Variant PNRC1:p.Ala107Gly (chr6-89081214-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006813.3(PNRC1):c.320C>G(p.Ala107Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000706 in 1,558,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

PNRC1
NM_006813.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.47

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 made for transcript

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=0.091438234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNRC1	NM_006813.3 link	c.320C>G	p.Ala107Gly	missense_variant	Exon 1 of 2	ENST00000336032.4	NP_006804.1	Q12796-1
PNRC1	XM_047418106.1 link	c.320C>G	p.Ala107Gly	missense_variant	Exon 1 of 2		XP_047274062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNRC1	ENST00000336032.4 link	c.320C>G	p.Ala107Gly	missense_variant	Exon 1 of 2	1	NM_006813.3	ENSP00000336931.3		Q12796-1
PNRC1	ENST00000369472.1 link	c.-16+241C>G		intron_variant	Intron 1 of 1	2		ENSP00000358484.1		Q49A59

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000125

AC:

AN:

160028

Hom.:

AF XY:

0.0000225

AC XY:

AN XY:

89068

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000146

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000498

AC:

AN:

1406440

Hom.:

Cov.:

AF XY:

0.00000861

AC XY:

AN XY:

696930

show subpopulations

Gnomad4 AFR exome

AF:

0.0000310

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:

0.00000458

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.00000890

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 31, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.320C>G (p.A107G) alteration is located in exon 1 (coding exon 1) of the PNRC1 gene. This alteration results from a C to G substitution at nucleotide position 320, causing the alanine (A) at amino acid position 107 to be replaced by a glycine (G). 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

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.084

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.091

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.9

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.90

REVEL

Benign

0.095

Sift

Uncertain

0.028

Sift4G

Benign

0.081

Polyphen

0.14

Vest4

0.28

MutPred

0.17

Gain of relative solvent accessibility (P = 0.0023);

MVP

0.21

MPC

0.72

ClinPred

0.43

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.18

gMVP

0.10

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over