16-27884552-G-A

Position:

• chr16-27884552-G-A

Variant summary

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

The NM_001109763.2(GSG1L):​c.484C>T​(p.His162Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000164 in 1,461,548 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: GSG1L NM_001109763.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.10

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSG1L	NM_001109763.2	c.484C>T	p.His162Tyr	missense_variant	3/7	ENST00000447459.7	NP_001103233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSG1L	ENST00000447459.7	c.484C>T	p.His162Tyr	missense_variant	3/7	2	NM_001109763.2	ENSP00000394954	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461548 Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13 AN XY: 727006

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 11, 2024

The c.484C>T (p.H162Y) alteration is located in exon 3 (coding exon 3) of the GSG1L gene. This alteration results from a C to T substitution at nucleotide position 484, causing the histidine (H) at amino acid position 162 to be replaced by a tyrosine (Y). 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	0.22
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T;.;.
Eigen	Benign	0.16
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.84	T;T;T
M_CAP	Benign	0.0097	T
MetaRNN	Uncertain	0.49	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.49	N;.;.
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.13
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.94	P;.;B
Vest4		0.82
MVP		0.32
MPC		1.1
ClinPred		0.68	D
GERP RS		5.3
Varity_R		0.094
gMVP		0.68

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

Other links and lift over

dbSNP: rs146616399; hg19: chr16-27895873;