rs1386645292

Variant names:

• chr16-27884519-T-C
• rs1386645292
• NM_001109763.2:c.517A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-27884519-T-C
• chr16-27884519-T-G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001109763.2(GSG1L):​c.517A>G​(p.Asn173Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: GSG1L NM_001109763.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.95
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772

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.517A>G	p.Asn173Asp	missense	Exon 3 of 7	NP_001103233.1	Q6UXU4-1
	GSG1L	NM_001323900.2		c.517A>G	p.Asn173Asp	missense	Exon 3 of 8	NP_001310829.1
	GSG1L	NM_144675.3		c.52A>G	p.Asn18Asp	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.517A>G	p.Asn173Asp	missense	Exon 3 of 7	ENSP00000394954.2	Q6UXU4-1
	GSG1L	ENST00000569166.1	TSL:1	c.52A>G	p.Asn18Asp	missense	Exon 1 of 6	ENSP00000454880.1	Q6UXU4-4
	GSG1L	ENST00000380897.7	TSL:1	c.52A>G	p.Asn18Asp	missense	Exon 2 of 6	ENSP00000370282.3	Q6UXU4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 250986 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461676 Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11 AN XY: 727100

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

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53366

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

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111932

Other (OTH) AF: 0.0000497 AC: 3 AN: 60386

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	Pathogenic	0.98
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.017	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.97	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.88	D
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.26
Sift	Benign	0.33	T
Sift4G	Benign	0.29	T
Polyphen		1.0	D
Vest4		0.96
MutPred		0.47		Gain of ubiquitination at K171 (P = 0.0822)
MVP		0.62
MPC		0.83
ClinPred		0.68	D
GERP RS		5.2
PromoterAI		0.0013	Neutral
Varity_R		0.33
gMVP		0.97
Mutation Taster		=32/68	disease causing

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: rs1386645292; hg19: chr16-27895840;