Variant 16-27791401-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001109763.2(GSG1L):c.965G>A(p.Arg322Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,364,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

GSG1L
NM_001109763.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14711091).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GSG1L	NM_001109763.2 linkuse as main transcript	c.965G>A	p.Arg322Gln	missense_variant	7/7	ENST00000447459.7	NP_001103233.1
GSG1L	NM_001323900.2 linkuse as main transcript	c.1019G>A	p.Arg340Gln	missense_variant	8/8		NP_001310829.1
GSG1L	NM_001323901.2 linkuse as main transcript	c.812G>A	p.Arg271Gln	missense_variant	6/6		NP_001310830.1
GSG1L	NM_144675.3 linkuse as main transcript	c.500G>A	p.Arg167Gln	missense_variant	6/6		NP_653276.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSG1L	ENST00000447459.7 linkuse as main transcript	c.965G>A	p.Arg322Gln	missense_variant	7/7	2	NM_001109763.2	ENSP00000394954	P1	Q6UXU4-1
GSG1L	ENST00000395724.7 linkuse as main transcript	c.812G>A	p.Arg271Gln	missense_variant	6/6	1		ENSP00000379074		Q6UXU4-3
GSG1L	ENST00000569166.1 linkuse as main transcript	c.554G>A	p.Arg185Gln	missense_variant	6/6	1		ENSP00000454880		Q6UXU4-4
GSG1L	ENST00000380897.7 linkuse as main transcript	c.500G>A	p.Arg167Gln	missense_variant	6/6	1		ENSP00000370282		Q6UXU4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000364

AC:

AN:

192054

Hom.:

AF XY:

0.0000481

AC XY:

AN XY:

103990

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.0000413

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000956

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000333

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1364140

Hom.:

Cov.:

AF XY:

0.0000163

AC XY:

AN XY:

673426

show subpopulations

Gnomad4 AFR exome

AF:

0.0000335

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000826

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000661

Gnomad4 OTH exome

AF:

0.0000180

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Mar 06, 2023

The c.965G>A (p.R322Q) alteration is located in exon 7 (coding exon 7) of the GSG1L gene. This alteration results from a G to A substitution at nucleotide position 965, causing the arginine (R) at amino acid position 322 to be replaced by a glutamine (Q). 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

0.087

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0022

T;.;.;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.;.;.

MutationTaster

Benign

0.90

N;N;N;N;N

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.20

N;N;N;N

REVEL

Benign

0.16

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

0.16

T;T;T;T

Polyphen

0.98

D;D;.;P

Vest4

0.38

MVP

0.35

MPC

0.54

ClinPred

0.17

GERP RS

3.0

Varity_R

0.23

gMVP

0.13

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