NM_002066.3:c.379G>A

Variant names:

• chr8-142846592-G-A
• NM_002066.3:c.379G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002066.3(GML):​c.379G>A​(p.Val127Ile) 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GML NM_002066.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.44
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046549648).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002066.3. 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
	GML	NM_002066.3	MANE Select	c.379G>A	p.Val127Ile	missense	Exon 4 of 4	NP_002057.1	Q99445

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GML	ENST00000220940.2	TSL:1 MANE Select	c.379G>A	p.Val127Ile	missense	Exon 4 of 4	ENSP00000220940.1	Q99445
	GML	ENST00000522728.5	TSL:3	c.181+5367G>A		intron	N/A	ENSP00000430799.1	E5RI31

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Benign	0.085
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.0020
DANN	Benign	0.37
DEOGEN2	Benign	0.011	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-2.4
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.031
Sift	Benign	0.44	T
Sift4G	Benign	0.47	T
Polyphen		0.0	B
Vest4		0.043
MutPred		0.096		Gain of catalytic residue at L132 (P = 0.0562)
MVP		0.17
MPC		0.13
ClinPred		0.50	D
GERP RS		-7.0
Varity_R		0.022
gMVP		0.13
Mutation Taster		=99/1	polymorphism

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

hg19: chr8-143928008;