16-27828791-C-G

Variant names:

• chr16-27828791-C-G
• rs752508560
• NM_001109763.2:c.828G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001109763.2(GSG1L):​c.828G>C​(p.Glu276Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GSG1L NM_001109763.2 missense, splice_region
• Scores: Splicing: ADA: 0.3247
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.06

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]

ACMG classification

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=0.17665792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSG1L	NM_001109763.2	c.828G>C	p.Glu276Asp	missense_variant, splice_region_variant	Exon 5 of 7	ENST00000447459.7	NP_001103233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSG1L	ENST00000447459.7	c.828G>C	p.Glu276Asp	missense_variant, splice_region_variant	Exon 5 of 7	2	NM_001109763.2	ENSP00000394954.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.828G>C (p.E276D) alteration is located in exon 5 (coding exon 5) of the GSG1L gene. This alteration results from a G to C substitution at nucleotide position 828, causing the glutamic acid (E) at amino acid position 276 to be replaced by an aspartic acid (D). 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	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0059	T;.;.;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.0084
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.61	T;T;T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;.;.;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.48	N;N;N;N
REVEL	Benign	0.043
Sift	Benign	0.18	T;T;T;T
Sift4G	Benign	0.26	T;T;T;T
Polyphen		0.0010	B;B;.;B
Vest4		0.24
MutPred		0.098		Loss of phosphorylation at Y273 (P = 0.0854);.;.;.;
MVP		0.20
MPC		0.42
ClinPred		0.75	D
GERP RS		4.2
Varity_R		0.092
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.32
dbscSNV1_RF	Benign	0.42
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

Other links and lift over

dbSNP: rs752508560; hg19: chr16-27840112;