chr8-142841217-T-C

Variant names:

• chr8-142841217-T-C
• rs765865698
• NM_002066.3:c.173T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002066.3(GML):​c.173T>C​(p.Ile58Thr) 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. 13/22 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. I58N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GML NM_002066.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85
• 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: 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=0.12854448).

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.173T>C	p.Ile58Thr	missense	Exon 3 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.173T>C	p.Ile58Thr	missense	Exon 3 of 4	ENSP00000220940.1	Q99445
	GML	ENST00000522728.5	TSL:3	c.173T>C	p.Ile58Thr	missense	Exon 3 of 5	ENSP00000430799.1	E5RI31

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1288720 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 650086

African (AFR) AF: 0.00 AC: 0 AN: 29742

American (AMR) AF: 0.00 AC: 0 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25004

East Asian (EAS) AF: 0.00 AC: 0 AN: 38532

South Asian (SAS) AF: 0.00 AC: 0 AN: 82476

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5464

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 955222

Other (OTH) AF: 0.00 AC: 0 AN: 54414

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000312 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.078	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.00069	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.9
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-4.2	D
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.013	D
Polyphen		0.40	B
Vest4		0.42
MutPred		0.47		Loss of stability (P = 0.0853)
MVP		0.15
MPC		0.29
ClinPred		0.54	D
GERP RS		3.4
Varity_R		0.13
gMVP		0.27
Mutation Taster		=98/2	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

dbSNP: rs765865698; hg19: chr8-143922633;