Genetic Variant NM_001109763.2:c.917C>T (chr16-27791449-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001109763.2(GSG1L):c.917C>T(p.Ala306Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,500,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

GSG1L
NM_001109763.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.255

Publications

3 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017878681).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001109763.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GSG1L	NM_001109763.2	MANE Select	c.917C>T	p.Ala306Val	missense	Exon 7 of 7	NP_001103233.1	Q6UXU4-1
GSG1L	NM_001323900.2		c.971C>T	p.Ala324Val	missense	Exon 8 of 8	NP_001310829.1
GSG1L	NM_001323901.2		c.764C>T	p.Ala255Val	missense	Exon 6 of 6	NP_001310830.1	Q6UXU4-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GSG1L	ENST00000447459.7	TSL:2 MANE Select	c.917C>T	p.Ala306Val	missense	Exon 7 of 7	ENSP00000394954.2	Q6UXU4-1
GSG1L	ENST00000395724.7	TSL:1	c.764C>T	p.Ala255Val	missense	Exon 6 of 6	ENSP00000379074.3	Q6UXU4-3
GSG1L	ENST00000569166.1	TSL:1	c.506C>T	p.Ala169Val	missense	Exon 6 of 6	ENSP00000454880.1	Q6UXU4-4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000443

AC:

AN:

180642

AF XY:

0.0000410

show subpopulations

Gnomad AFR exome

AF:

0.000158

Gnomad AMR exome

AF:

0.0000880

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000470

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000208

AC:

AN:

1348748

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

665094

show subpopulations

African (AFR)

AF:

0.000170

AC:

AN:

29406

American (AMR)

AF:

0.0000303

AC:

AN:

32992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21570

East Asian (EAS)

AF:

0.0000294

AC:

AN:

34056

South Asian (SAS)

AF:

0.0000143

AC:

AN:

70070

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50718

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4616

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1050318

Other (OTH)

AF:

0.0000364

AC:

AN:

55002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.405

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41532

American (AMR)

AF:

0.0000654

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000495

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.0022

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.52

M_CAP

Benign

0.0089

MetaRNN

Benign

0.018

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

PhyloP100

-0.26

PrimateAI

Uncertain

0.62

PROVEAN

Benign

0.95

REVEL

Benign

0.023

Sift

Benign

0.32

Sift4G

Benign

0.26

Polyphen

0.084

Vest4

0.050

MVP

0.44

MPC

0.45

ClinPred

0.017

GERP RS

-4.0

Varity_R

0.026

gMVP

0.25

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over