Genetic Variant GSG1L:p.Thr236Ser (chr16-27828912-G-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001109763.2(GSG1L):c.707C>G(p.Thr236Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T236I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

GSG1L
NM_001109763.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.95

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.707C>G	p.Thr236Ser	missense	Exon 5 of 7	NP_001103233.1	Q6UXU4-1
GSG1L	NM_001323900.2		c.707C>G	p.Thr236Ser	missense	Exon 5 of 8	NP_001310829.1
GSG1L	NM_001323901.2		c.554C>G	p.Thr185Ser	missense	Exon 4 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.707C>G	p.Thr236Ser	missense	Exon 5 of 7	ENSP00000394954.2	Q6UXU4-1
GSG1L	ENST00000395724.7	TSL:1	c.554C>G	p.Thr185Ser	missense	Exon 4 of 6	ENSP00000379074.3	Q6UXU4-3
GSG1L	ENST00000569166.1	TSL:1	c.242C>G	p.Thr81Ser	missense	Exon 3 of 6	ENSP00000454880.1	Q6UXU4-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251404

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.0000671

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.86

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.66

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

6.9

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.19

Sift

Benign

0.073

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.72

MutPred

0.29

Gain of disorder (P = 0.1934)

MVP

0.38

MPC

1.2

ClinPred

0.98

GERP RS

5.3

Varity_R

0.35

gMVP

0.86

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over