chr16-28063180-G-A

Variant names:

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

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.245C>T​(p.Pro82Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000848 in 1,179,288 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P82R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: GSG1L NM_001109763.2 missense
• Clinical Significance: Not reported in ClinVar
• 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: 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=0.18915927).

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>T	p.Pro82Leu	missense	Exon 1 of 7	NP_001103233.1	Q6UXU4-1
	GSG1L	NM_001323900.2		c.245C>T	p.Pro82Leu	missense	Exon 1 of 8	NP_001310829.1
	GSG1L	NM_001323901.2		c.245C>T	p.Pro82Leu	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>T	p.Pro82Leu	missense	Exon 1 of 7	ENSP00000394954.2	Q6UXU4-1
	GSG1L	ENST00000395724.7	TSL:1	c.245C>T	p.Pro82Leu	missense	Exon 1 of 6	ENSP00000379074.3	Q6UXU4-3
	GSG1L	ENST00000951031.1		c.245C>T	p.Pro82Leu	missense	Exon 1 of 7	ENSP00000621090.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.48e-7 AC: 1 AN: 1179288 Hom.: 0 Cov.: 31 AF XY: 0.00000173 AC XY: 1 AN XY: 576368

African (AFR) AF: 0.00 AC: 0 AN: 24122

American (AMR) AF: 0.00 AC: 0 AN: 16060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18412

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 45588

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29962

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4490

European-Non Finnish (NFE) AF: 0.00000103 AC: 1 AN: 969268

Other (OTH) AF: 0.00 AC: 0 AN: 46740

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.59	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.017
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.035
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.024	D
Polyphen		0.61	P
Vest4		0.11
MutPred		0.42		Loss of glycosylation at P82 (P = 0.0063)
MVP		0.23
MPC		0.65
ClinPred		0.75	D
GERP RS		0.88
PromoterAI		0.0091	Neutral
Varity_R		0.088
gMVP		0.24

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;