16-27884519-T-G

Variant names:

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

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>C​(p.Asn173His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. N173D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GSG1L NM_001109763.2 missense
• Clinical Significance: Not reported in ClinVar
• 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, 0.818

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>C	p.Asn173His	missense	Exon 3 of 7	NP_001103233.1	Q6UXU4-1
	GSG1L	NM_001323900.2		c.517A>C	p.Asn173His	missense	Exon 3 of 8	NP_001310829.1
	GSG1L	NM_144675.3		c.52A>C	p.Asn18His	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>C	p.Asn173His	missense	Exon 3 of 7	ENSP00000394954.2	Q6UXU4-1
	GSG1L	ENST00000569166.1	TSL:1	c.52A>C	p.Asn18His	missense	Exon 1 of 6	ENSP00000454880.1	Q6UXU4-4
	GSG1L	ENST00000380897.7	TSL:1	c.52A>C	p.Asn18His	missense	Exon 2 of 6	ENSP00000370282.3	Q6UXU4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461676 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 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: 8.99e-7 AC: 1 AN: 1111932

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	2.0	M
PhyloP100		7.9
PrimateAI	Pathogenic	0.86	D
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.96
MutPred		0.43		Loss of catalytic residue at N173 (P = 0.0272)
MVP		0.66
MPC		1.4
ClinPred		0.99	D
GERP RS		5.2
PromoterAI		-0.032	Neutral
Varity_R		0.35
gMVP		0.93
Mutation Taster		=29/71	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;