Variant 11-62707720-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_012202.5(GNG3):c.-197G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 325,964 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0099 ( 11 hom., cov: 33)

Exomes 𝑓: 0.016 ( 41 hom. )

Consequence

GNG3
NM_012202.5 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.434

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:):

HNRNPUL2-BSCL2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 11-62707720-G-A is Benign according to our data. Variant chr11-62707720-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1198651.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00988 (1505/152328) while in subpopulation SAS AF= 0.0358 (173/4828). AF 95% confidence interval is 0.0315. There are 11 homozygotes in gnomad4. There are 806 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1505 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GNG3	NM_012202.5 linkuse as main transcript	c.-197G>A		5_prime_UTR_variant	1/3	ENST00000294117.6
HNRNPUL2-BSCL2	NR_037946.1 linkuse as main transcript	n.2392-396C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GNG3	ENST00000294117.6 linkuse as main transcript	c.-197G>A		5_prime_UTR_variant	1/3	1	NM_012202.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00987

AC:

1503

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00188

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.0282

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0354

Gnomad FIN

AF:

0.0186

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0128

Gnomad OTH

AF:

0.00908

GnomAD4 exome

AF:

0.0158

AC:

2745

AN:

173636

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

1648

AN XY:

93344

show subpopulations

Gnomad4 AFR exome

AF:

0.00135

Gnomad4 AMR exome

AF:

0.00285

Gnomad4 ASJ exome

AF:

0.0348

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0346

Gnomad4 FIN exome

AF:

0.0177

Gnomad4 NFE exome

AF:

0.0129

Gnomad4 OTH exome

AF:

0.0143

GnomAD4 genome

AF:

0.00988

AC:

1505

AN:

152328

Hom.:

Cov.:

AF XY:

0.0108

AC XY:

806

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00188

Gnomad4 AMR

AF:

0.00373

Gnomad4 ASJ

AF:

0.0282

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0358

Gnomad4 FIN

AF:

0.0186

Gnomad4 NFE

AF:

0.0128

Gnomad4 OTH

AF:

0.00899

Alfa

AF:

0.0118

Hom.:

Bravo

AF:

0.00743

Asia WGS

AF:

0.0130

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

Jul 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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