Variant 16-28063180-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001109763.2(GSG1L):c.245C>G(p.Pro82Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000393 in 1,330,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 0 hom. )

Consequence

GSG1L
NM_001109763.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0170

Variant links:

Genes affected

GSG1L (HGNC:28283): (GSG1 like) Predicted to be involved in regulation of AMPA receptor activity. Predicted to be located in postsynaptic density. Predicted to be active in Schaffer collateral - CA1 synapse; glutamatergic synapse; and plasma membrane. Predicted to be integral component of postsynaptic density membrane. [provided by Alliance of Genome Resources, Apr 2022]

GSG1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04684791).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSG1L	NM_001109763.2 linkuse as main transcript	c.245C>G	p.Pro82Arg	missense_variant	1/7	ENST00000447459.7	NP_001103233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSG1L	ENST00000447459.7 linkuse as main transcript	c.245C>G	p.Pro82Arg	missense_variant	1/7	2	NM_001109763.2	ENSP00000394954	P1	Q6UXU4-1
GSG1L	ENST00000395724.7 linkuse as main transcript	c.245C>G	p.Pro82Arg	missense_variant	1/6	1		ENSP00000379074		Q6UXU4-3
GSG1L	ENST00000562611.1 linkuse as main transcript	c.11C>G	p.Pro4Arg	missense_variant, NMD_transcript_variant	1/7	3		ENSP00000454942

Frequencies

GnomAD3 genomes

AF:

0.000403

AC:

AN:

151190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000659

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000985

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000649

Gnomad OTH

AF:

0.000483

GnomAD3 exomes

AF:

0.000294

AC:

AN:

54354

Hom.:

AF XY:

0.000216

AC XY:

AN XY:

32358

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000151

Gnomad ASJ exome

AF:

0.000937

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000459

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000392

AC:

462

AN:

1179288

Hom.:

Cov.:

AF XY:

0.000418

AC XY:

241

AN XY:

576368

show subpopulations

Gnomad4 AFR exome

AF:

0.0000415

Gnomad4 AMR exome

AF:

0.000125

Gnomad4 ASJ exome

AF:

0.00158

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000439

Gnomad4 FIN exome

AF:

0.000234

Gnomad4 NFE exome

AF:

0.000401

Gnomad4 OTH exome

AF:

0.000642

GnomAD4 genome

AF:

0.000403

AC:

AN:

151298

Hom.:

Cov.:

AF XY:

0.000419

AC XY:

AN XY:

73940

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000658

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000985

Gnomad4 NFE

AF:

0.000650

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000424

Hom.:

Bravo

AF:

0.000321

ExAC

AF:

0.0000550

AC:

Asia WGS

AF:

0.000306

AC:

AN:

3278

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

The c.245C>G (p.P82R) alteration is located in exon 1 (coding exon 1) of the GSG1L gene. This alteration results from a C to G substitution at nucleotide position 245, causing the proline (P) at amino acid position 82 to be replaced by an arginine (R). 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

0.088

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.013

T;.

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.47

T;T

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.047

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

0.93

D;D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.036

Sift

Uncertain

0.0060

D;D

Sift4G

Uncertain

0.035

D;D

Polyphen

0.73

P;P

Vest4

0.11

MVP

0.16

MPC

0.76

ClinPred

0.089

GERP RS

0.88

Varity_R

0.14

gMVP

0.15

Splicing

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