dbSNP rs3749147: GPN1:p.Arg12Lys (chr2-27629051-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000264718.7(GPN1):c.35G>A(p.Arg12Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,613,938 control chromosomes in the GnomAD database, including 50,452 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3790 hom., cov: 32)

Exomes 𝑓: 0.25 ( 46662 hom. )

Consequence

GPN1
ENST00000264718.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.742

Variant links:

Genes affected

GPN1 (HGNC:17030): (GPN-loop GTPase 1) This gene encodes a guanosine triphosphatase enzyme. The encoded protein may play a role in DNA repair and may function in activation of transcription. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2009]

GPN1 links:

ENSG00000259080 (HGNC:):

ENSG00000259080 links:

CCDC121 (HGNC:25833): (coiled-coil domain containing 121)

CCDC121 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043020844).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPN1	NM_007266.4 link	c.-8G>A		5_prime_UTR_variant	Exon 1 of 14	ENST00000610189.2	NP_009197.3	Q9HCN4-1Q53RZ9
CCDC121	NM_024584.5 link	c.-220C>T		upstream_gene_variant		ENST00000324364.4	NP_078860.2	Q6ZUS5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPN1	ENST00000610189 link	c.-8G>A		5_prime_UTR_variant	Exon 1 of 14	1	NM_007266.4	ENSP00000476446.1		Q9HCN4-1
CCDC121	ENST00000324364.4 link	c.-220C>T		upstream_gene_variant		1	NM_024584.5	ENSP00000339087.2		Q6ZUS5-1

Frequencies

GnomAD3 genomes

AF:

0.203

AC:

30876

AN:

152098

Hom.:

3791

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0642

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.307

Gnomad SAS

AF:

0.179

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.264

Gnomad OTH

AF:

0.250

GnomAD3 exomes

AF:

0.229

AC:

57492

AN:

251142

Hom.:

7395

AF XY:

0.234

AC XY:

31711

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.0576

Gnomad AMR exome

AF:

0.139

Gnomad ASJ exome

AF:

0.345

Gnomad EAS exome

AF:

0.309

Gnomad SAS exome

AF:

0.185

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.263

Gnomad OTH exome

AF:

0.257

GnomAD4 exome

AF:

0.247

AC:

361611

AN:

1461722

Hom.:

46662

Cov.:

AF XY:

0.247

AC XY:

179937

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.0559

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.342

Gnomad4 EAS exome

AF:

0.348

Gnomad4 SAS exome

AF:

0.187

Gnomad4 FIN exome

AF:

0.249

Gnomad4 NFE exome

AF:

0.256

Gnomad4 OTH exome

AF:

0.251

GnomAD4 genome

AF:

0.203

AC:

30872

AN:

152216

Hom.:

3790

Cov.:

AF XY:

0.203

AC XY:

15136

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0640

Gnomad4 AMR

AF:

0.203

Gnomad4 ASJ

AF:

0.345

Gnomad4 EAS

AF:

0.307

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.258

Gnomad4 NFE

AF:

0.264

Gnomad4 OTH

AF:

0.252

Alfa

AF:

0.255

Hom.:

8508

Bravo

AF:

0.192

TwinsUK

AF:

0.251

AC:

931

ALSPAC

AF:

0.249

AC:

961

ESP6500AA

AF:

0.0663

AC:

292

ESP6500EA

AF:

0.265

AC:

2283

ExAC

AF:

0.225

AC:

27292

Asia WGS

AF:

0.202

AC:

703

AN:

3478

EpiCase

AF:

0.287

EpiControl

AF:

0.287

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.91

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.41

T;.

MetaRNN

Benign

0.0043

T;T

MetaSVM

Benign

-0.96

PrimateAI

Uncertain

0.61

PROVEAN

Benign

0.040

.;N

REVEL

Benign

0.031

Sift

Benign

0.63

.;T

Sift4G

Benign

0.90

T;T

Vest4

0.11

MPC

0.21

ClinPred

0.0038

GERP RS

1.9

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over