16-28063180-G-C

Variant names:

• chr16-28063180-G-C
• rs573639761
• NM_001109763.2:c.245C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001109763.2(GSG1L):​c.245C>G​(p.Pro82Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000393 in 1,330,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (0 hom.)
• Consequence: GSG1L NM_001109763.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0170
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04684791).

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.245C>G	p.Pro82Arg	missense	Exon 1 of 7	NP_001103233.1	Q6UXU4-1
	GSG1L	NM_001323900.2		c.245C>G	p.Pro82Arg	missense	Exon 1 of 8	NP_001310829.1
	GSG1L	NM_001323901.2		c.245C>G	p.Pro82Arg	missense	Exon 1 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.245C>G	p.Pro82Arg	missense	Exon 1 of 7	ENSP00000394954.2	Q6UXU4-1
	GSG1L	ENST00000395724.7	TSL:1	c.245C>G	p.Pro82Arg	missense	Exon 1 of 6	ENSP00000379074.3	Q6UXU4-3
	GSG1L	ENST00000951031.1		c.245C>G	p.Pro82Arg	missense	Exon 1 of 7	ENSP00000621090.1

Frequencies

GnomAD3 genomes AF: 0.000403 AC: 61 AN: 151190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000659

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000985

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000649

Gnomad OTH AF: 0.000483

GnomAD2 exomes AF: 0.000294 AC: 16 AN: 54354 AF XY: 0.000216

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000151

Gnomad ASJ exome AF: 0.000937

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000459

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000392 AC: 462 AN: 1179288 Hom.: 0 Cov.: 31 AF XY: 0.000418 AC XY: 241 AN XY: 576368

African (AFR) AF: 0.0000415 AC: 1 AN: 24122

American (AMR) AF: 0.000125 AC: 2 AN: 16060

Ashkenazi Jewish (ASJ) AF: 0.00158 AC: 29 AN: 18412

East Asian (EAS) AF: 0.00 AC: 0 AN: 24646

South Asian (SAS) AF: 0.0000439 AC: 2 AN: 45588

European-Finnish (FIN) AF: 0.000234 AC: 7 AN: 29962

Middle Eastern (MID) AF: 0.000445 AC: 2 AN: 4490

European-Non Finnish (NFE) AF: 0.000401 AC: 389 AN: 969268

Other (OTH) AF: 0.000642 AC: 30 AN: 46740

GnomAD4 genome AF: 0.000403 AC: 61 AN: 151298 Hom.: 0 Cov.: 32 AF XY: 0.000419 AC XY: 31 AN XY: 73940

African (AFR) AF: 0.0000483 AC: 2 AN: 41444

American (AMR) AF: 0.000658 AC: 10 AN: 15206

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 3 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000985 AC: 1 AN: 10156

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000650 AC: 44 AN: 67742

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.000424 Hom.: 0

Bravo AF: 0.000321

ExAC AF: 0.0000550 AC: 1

Asia WGS AF: 0.000306 AC: 1 AN: 3278

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	0.088
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.27	D
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.017
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.036
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.035	D
Polyphen		0.73	P
Vest4		0.11
MVP		0.16
MPC		0.76
ClinPred		0.089	T
GERP RS		0.88
PromoterAI		-0.051	Neutral
Varity_R		0.14
gMVP		0.15
Mutation Taster		=91/9	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs573639761; hg19: chr16-28074501;