Genetic Variant GPN1:c.*259C>G (chr2-27650459-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007266.4(GPN1):c.*259C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 221,554 control chromosomes in the GnomAD database, including 7,788 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 0.23 ( 4886 hom., cov: 32)

Exomes 𝑓: 0.26 ( 2902 hom. )

Consequence

GPN1
NM_007266.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0260

Publications

16 publications found

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:

SUPT7L (HGNC:30632): (SPT7 like, STAGA complex subunit gamma) SUPT7L is a protein subunit of the human STAGA complex (SPT3; (MIM 602947)/TAF9 (MIM 600822)/GCN5 (MIM 602301) acetyltransferase complex), which is a chromatin-modifying multiprotein complex (Martinez et al., 2001 [PubMed 11564863]).[supplied by OMIM, Apr 2009]

SUPT7L Gene-Disease associations (from GenCC):

lipodystrophy
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

SUPT7L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPN1	NM_007266.4 link	c.*259C>G		3_prime_UTR_variant	Exon 14 of 14	ENST00000610189.2	NP_009197.3	Q9HCN4-1Q53RZ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPN1	ENST00000610189.2 link	c.*259C>G		3_prime_UTR_variant	Exon 14 of 14	1	NM_007266.4	ENSP00000476446.1		Q9HCN4-1

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

35009

AN:

151992

Hom.:

4879

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.370

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.574

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.243

GnomAD4 exome

AF:

0.265

AC:

18402

AN:

69444

Hom.:

2902

Cov.:

AF XY:

0.265

AC XY:

9397

AN XY:

35480

show subpopulations

African (AFR)

AF:

0.137

AC:

314

AN:

2300

American (AMR)

AF:

0.428

AC:

1283

AN:

2996

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

591

AN:

2622

East Asian (EAS)

AF:

0.529

AC:

3214

AN:

6076

South Asian (SAS)

AF:

0.313

AC:

1072

AN:

3420

European-Finnish (FIN)

AF:

0.250

AC:

920

AN:

3678

Middle Eastern (MID)

AF:

0.178

AC:

AN:

298

European-Non Finnish (NFE)

AF:

0.225

AC:

9801

AN:

43566

Other (OTH)

AF:

0.257

AC:

1154

AN:

4488

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

647

1294

1941

2588

3235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<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:

0.230

AC:

35040

AN:

152110

Hom.:

4886

Cov.:

AF XY:

0.237

AC XY:

17647

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.142

AC:

5897

AN:

41524

American (AMR)

AF:

0.383

AC:

5850

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

715

AN:

3468

East Asian (EAS)

AF:

0.574

AC:

2972

AN:

5174

South Asian (SAS)

AF:

0.318

AC:

1535

AN:

4820

European-Finnish (FIN)

AF:

0.231

AC:

2443

AN:

10558

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.217

AC:

14732

AN:

67970

Other (OTH)

AF:

0.242

AC:

511

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1302

2604

3906

5208

6510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

360

720

1080

1440

1800

<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:

0.223

Hom.:

552

Bravo

AF:

0.243

Asia WGS

AF:

0.434

AC:

1505

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.7

(source)

DANN

Benign

0.49

PhyloP100

0.026

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