Variant 11-62708185-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_012202.5(GNG3):c.-1-110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00476 in 773,240 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 28 hom. )

Consequence

GNG3
NM_012202.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.195

Variant links:

Genes affected

GNG3 (HGNC:4405): (G protein subunit gamma 3) Guanine nucleotide binding proteins are heterotrimeric signal-transducing molecules consisting of alpha, beta, and gamma subunits. The gamma subunit determines the specificity of which signaling pathways will be affected by this particular complex. The protein encoded by this gene represents the gamma subunit of both inhibitory and stimulatory complexes. [provided by RefSeq, Jan 2012]

GNG3 links:

BSCL2 (HGNC:15832): (BSCL2 lipid droplet biogenesis associated, seipin) This gene encodes the multi-pass transmembrane protein protein seipin. This protein localizes to the endoplasmic reticulum and may be important for lipid droplet morphology. Mutations in this gene have been associated with congenital generalized lipodystrophy type 2 or Berardinelli-Seip syndrome, a rare autosomal recessive disease characterized by a near absence of adipose tissue and severe insulin resistance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. Naturally occurring read-through transcription occurs between this locus and the neighboring locus HNRNPUL2 (heterogeneous nuclear ribonucleoprotein U-like 2).[provided by RefSeq, Mar 2011]

BSCL2 links:

HNRNPUL2-BSCL2 (HGNC:49189): (HNRNPUL2-BSCL2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring HNRNPUL2 (heterogeneous nuclear ribonucleoprotein U-like 2) and BSCL2 (Berardinelli-Seip congenital lipodystrophy 2 (seipin)) genes on chromosome 11. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

HNRNPUL2-BSCL2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 11-62708185-G-A is Benign according to our data. Variant chr11-62708185-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1321543.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 596 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GNG3	NM_012202.5 link	c.-1-110G>A		intron_variant		ENST00000294117.6	NP_036334.1	P63215

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GNG3	ENST00000294117.6 link	c.-1-110G>A		intron_variant		1	NM_012202.5	ENSP00000294117.5		P63215
HNRNPUL2-BSCL2	ENST00000403734.2 link	n.2164-861C>T		intron_variant		2		ENSP00000456010.1		H3BQZ7

Frequencies

GnomAD3 genomes

AF:

0.00392

AC:

596

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00620

Gnomad FIN

AF:

0.0148

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00559

Gnomad OTH

AF:

0.00144

GnomAD4 exome

AF:

0.00497

AC:

3084

AN:

620920

Hom.:

Cov.:

AF XY:

0.00527

AC XY:

1760

AN XY:

334226

show subpopulations

Gnomad4 AFR exome

AF:

0.000340

Gnomad4 AMR exome

AF:

0.000254

Gnomad4 ASJ exome

AF:

0.00206

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00617

Gnomad4 FIN exome

AF:

0.0130

Gnomad4 NFE exome

AF:

0.00520

Gnomad4 OTH exome

AF:

0.00324

GnomAD4 genome

AF:

0.00391

AC:

596

AN:

152320

Hom.:

Cov.:

AF XY:

0.00418

AC XY:

311

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00621

Gnomad4 FIN

AF:

0.0148

Gnomad4 NFE

AF:

0.00559

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00895

Hom.:

Bravo

AF:

0.00223

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.7

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.29

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.29

Position offset: 15

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