8-142841204-C-G

Position:

• chr8-142841204-C-G

Variant summary

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

The NM_002066.3(GML):​c.160C>G​(p.Arg54Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,356,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R54C) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: GML NM_002066.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GML	NM_002066.3	c.160C>G	p.Arg54Gly	missense_variant	3/4	ENST00000220940.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GML	ENST00000220940.2	c.160C>G	p.Arg54Gly	missense_variant	3/4	1	NM_002066.3	P1
GML	ENST00000522728.5	c.160C>G	p.Arg54Gly	missense_variant	3/5	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1356698 Hom.: 0 Cov.: 23 AF XY: 0.00000147 AC XY: 1 AN XY: 680764

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.83e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	0.99
Eigen	Benign	0.12
Eigen_PC	Benign	-0.017
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.57	T;T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	0.65	P
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-7.0	D;D
REVEL	Benign	0.16
Sift	Pathogenic	0.0	D;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	.;D
Vest4		0.44
MutPred		0.42		Loss of MoRF binding (P = 0.0256);Loss of MoRF binding (P = 0.0256);
MVP		0.31
MPC		0.75
ClinPred		0.99	D
GERP RS		2.5
Varity_R		0.24
gMVP		0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.27		Position offset: 21

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

Publications

LitVar

Other links and lift over

dbSNP: rs3764795; hg19: chr8-143922620;