16-27791401-C-T

Variant names:

• chr16-27791401-C-T
• rs577887323
• NM_001109763.2:c.965G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001109763.2(GSG1L):​c.965G>A​(p.Arg322Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000117 in 1,364,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: GSG1L NM_001109763.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55
• Publications: 2 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14711091).

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.965G>A	p.Arg322Gln	missense	Exon 7 of 7	NP_001103233.1	Q6UXU4-1
	GSG1L	NM_001323900.2		c.1019G>A	p.Arg340Gln	missense	Exon 8 of 8	NP_001310829.1
	GSG1L	NM_001323901.2		c.812G>A	p.Arg271Gln	missense	Exon 6 of 6	NP_001310830.1	Q6UXU4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSG1L	ENST00000447459.7	TSL:2 MANE Select	c.965G>A	p.Arg322Gln	missense	Exon 7 of 7	ENSP00000394954.2	Q6UXU4-1
	GSG1L	ENST00000395724.7	TSL:1	c.812G>A	p.Arg271Gln	missense	Exon 6 of 6	ENSP00000379074.3	Q6UXU4-3
	GSG1L	ENST00000569166.1	TSL:1	c.554G>A	p.Arg185Gln	missense	Exon 6 of 6	ENSP00000454880.1	Q6UXU4-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000364 AC: 7 AN: 192054 AF XY: 0.0000481

Gnomad AFR exome AF: 0.0000760

Gnomad AMR exome AF: 0.0000413

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000333

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000117 AC: 16 AN: 1364140 Hom.: 0 Cov.: 30 AF XY: 0.0000163 AC XY: 11 AN XY: 673426

African (AFR) AF: 0.0000335 AC: 1 AN: 29872

American (AMR) AF: 0.00 AC: 0 AN: 34624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22394

East Asian (EAS) AF: 0.00 AC: 0 AN: 34474

South Asian (SAS) AF: 0.0000826 AC: 6 AN: 72674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51322

Middle Eastern (MID) AF: 0.000250 AC: 1 AN: 4008

European-Non Finnish (NFE) AF: 0.00000661 AC: 7 AN: 1059142

Other (OTH) AF: 0.0000180 AC: 1 AN: 55630

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000412 AC: 5

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.087
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0022	T
Eigen	Benign	0.13
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.6
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.20	N
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.16	T
Polyphen		0.98	D
Vest4		0.38
MVP		0.35
MPC		0.54
ClinPred		0.17	T
GERP RS		3.0
Varity_R		0.23
gMVP		0.13
Mutation Taster		=87/13	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: rs577887323; hg19: chr16-27802722; COSMIC: COSV66580450;