rs762192392

Variant names:

• chr8-142840483-G-C
• rs762192392
• NM_002066.3:c.46G>C

Your query was ambiguous. Multiple possible variants found:

• chr8-142840483-G-C
• chr8-142840483-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002066.3(GML):​c.46G>C​(p.Ala16Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GML NM_002066.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930

Genes affected

GML (HGNC:4375): (glycosylphosphatidylinositol anchored molecule like) Predicted to be involved in DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; apoptotic process; and negative regulation of cell population proliferation. Predicted to be extrinsic component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13075373).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GML	NM_002066.3	c.46G>C	p.Ala16Pro	missense_variant	Exon 2 of 4	ENST00000220940.2	NP_002057.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GML	ENST00000220940.2	c.46G>C	p.Ala16Pro	missense_variant	Exon 2 of 4	1	NM_002066.3	ENSP00000220940.1
GML	ENST00000522728.5	c.46G>C	p.Ala16Pro	missense_variant	Exon 2 of 5	3		ENSP00000430799.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251300 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135848

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	4.5
DANN	Benign	0.83
DEOGEN2	Benign	0.015	.;T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.38	T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	.;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.70	N;N
REVEL	Benign	0.096
Sift	Benign	0.14	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.76	.;P
Vest4		0.23
MutPred		0.53		Gain of loop (P = 0.0321);Gain of loop (P = 0.0321);
MVP		0.66
MPC		0.20
ClinPred		0.035	T
GERP RS		1.5
Varity_R		0.094
gMVP		0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs762192392; hg19: chr8-143921899;