Genetic Variant GSG1L:p.Asp287Asn (chr16-27807526-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001109763.2(GSG1L):c.859G>A(p.Asp287Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,460,690 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: not found (cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

GSG1L
NM_001109763.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24

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=0.15428561).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSG1L	NM_001109763.2 link	c.859G>A	p.Asp287Asn	missense_variant	Exon 6 of 7	ENST00000447459.7	NP_001103233.1	Q6UXU4-1B3KY67

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GSG1L	ENST00000447459.7 link	c.859G>A	p.Asp287Asn	missense_variant	Exon 6 of 7	2	NM_001109763.2	ENSP00000394954.2	Q6UXU4-1
GSG1L	ENST00000395724.7 link	c.706G>A	p.Asp236Asn	missense_variant	Exon 5 of 6	1		ENSP00000379074.3	Q6UXU4-3
GSG1L	ENST00000569166.1 link	c.448G>A	p.Asp150Asn	missense_variant	Exon 5 of 6	1		ENSP00000454880.1	Q6UXU4-4
GSG1L	ENST00000380897.7 link	c.394G>A	p.Asp132Asn	missense_variant	Exon 5 of 6	1		ENSP00000370282.3	Q6UXU4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000362

AC:

AN:

248488

Hom.:

AF XY:

0.0000445

AC XY:

AN XY:

134822

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000263

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1460690

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726616

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.859G>A (p.D287N) alteration is located in exon 6 (coding exon 6) of the GSG1L gene. This alteration results from a G to A substitution at nucleotide position 859, causing the aspartic acid (D) at amino acid position 287 to be replaced by an asparagine (N). 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

0.086

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.46

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

T;.;.;.

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.84

T;D;T;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Benign

0.69

N;.;.;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.74

N;N;N;N

REVEL

Benign

0.081

Sift

Uncertain

0.0040

D;D;D;D

Sift4G

Uncertain

0.055

T;T;D;D

Polyphen

0.99

D;D;.;D

Vest4

0.49

MutPred

0.20

Loss of stability (P = 0.3939);.;.;.;

MVP

0.46

MPC

0.70

ClinPred

0.12

GERP RS

3.8

Varity_R

0.11

gMVP

0.40

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