rs146616399

Variant names:

• chr16-27884552-G-A
• rs146616399
• NM_001109763.2:c.484C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSG1L	NM_001109763.2	MANE Select	c.484C>T	p.His162Tyr	missense	Exon 3 of 7	NP_001103233.1	Q6UXU4-1
	GSG1L	NM_001323900.2		c.484C>T	p.His162Tyr	missense	Exon 3 of 8	NP_001310829.1
	GSG1L	NM_144675.3		c.19C>T	p.His7Tyr	missense	Exon 2 of 6	NP_653276.1	Q6UXU4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSG1L	ENST00000447459.7	TSL:2 MANE Select	c.484C>T	p.His162Tyr	missense	Exon 3 of 7	ENSP00000394954.2	Q6UXU4-1
	GSG1L	ENST00000569166.1	TSL:1	c.19C>T	p.His7Tyr	missense	Exon 1 of 6	ENSP00000454880.1	Q6UXU4-4
	GSG1L	ENST00000380897.7	TSL:1	c.19C>T	p.His7Tyr	missense	Exon 2 of 6	ENSP00000370282.3	Q6UXU4-2

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

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000207 AC: 23 AN: 1111872

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000756

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0097	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.49	N
PhyloP100		8.1
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.94	P
Vest4		0.82
MVP		0.32
MPC		1.1
ClinPred		0.68	D
GERP RS		5.3
PromoterAI		-0.0083	Neutral
Varity_R		0.094
gMVP		0.68
Mutation Taster		=55/45	polymorphism

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

Other links and lift over

dbSNP: rs146616399; hg19: chr16-27895873;