Variant 8-142841204-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002066.3(GML):c.160C>T(p.Arg54Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.079 in 1,506,976 control chromosomes in the GnomAD database, including 9,953 homozygotes. 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.11 ( 1519 hom., cov: 33)

Exomes 𝑓: 0.075 ( 8434 hom. )

Consequence

GML
NM_002066.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.663

Variant links:

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]

GML links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GML	NM_002066.3 linkuse as main transcript	c.160C>T	p.Arg54Cys	missense_variant	3/4	ENST00000220940.2	NP_002057.1	Q99445

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GML	ENST00000220940.2 linkuse as main transcript	c.160C>T	p.Arg54Cys	missense_variant	3/4	1	NM_002066.3	ENSP00000220940.1		Q99445
GML	ENST00000522728.5 linkuse as main transcript	c.160C>T	p.Arg54Cys	missense_variant	3/5	3		ENSP00000430799.1		E5RI31

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16819

AN:

152042

Hom.:

1512

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.0983

Gnomad EAS

AF:

0.480

Gnomad SAS

AF:

0.189

Gnomad FIN

AF:

0.0800

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0551

Gnomad OTH

AF:

0.102

GnomAD3 exomes

AF:

0.127

AC:

31898

AN:

251266

Hom.:

3673

AF XY:

0.124

AC XY:

16801

AN XY:

135804

show subpopulations

Gnomad AFR exome

AF:

0.163

Gnomad AMR exome

AF:

0.159

Gnomad ASJ exome

AF:

0.0841

Gnomad EAS exome

AF:

0.484

Gnomad SAS exome

AF:

0.182

Gnomad FIN exome

AF:

0.0891

Gnomad NFE exome

AF:

0.0523

Gnomad OTH exome

AF:

0.0946

GnomAD4 exome

AF:

0.0755

AC:

102253

AN:

1354814

Hom.:

8434

Cov.:

AF XY:

0.0789

AC XY:

53622

AN XY:

679892

show subpopulations

Gnomad4 AFR exome

AF:

0.147

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.0835

Gnomad4 EAS exome

AF:

0.463

Gnomad4 SAS exome

AF:

0.180

Gnomad4 FIN exome

AF:

0.0898

Gnomad4 NFE exome

AF:

0.0448

Gnomad4 OTH exome

AF:

0.0890

GnomAD4 genome

AF:

0.111

AC:

16851

AN:

152162

Hom.:

1519

Cov.:

AF XY:

0.116

AC XY:

8647

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.131

Gnomad4 ASJ

AF:

0.0983

Gnomad4 EAS

AF:

0.480

Gnomad4 SAS

AF:

0.189

Gnomad4 FIN

AF:

0.0800

Gnomad4 NFE

AF:

0.0551

Gnomad4 OTH

AF:

0.102

Alfa

AF:

0.0710

Hom.:

1903

Bravo

AF:

0.115

TwinsUK

AF:

0.0480

AC:

178

ALSPAC

AF:

0.0501

AC:

193

ESP6500AA

AF:

0.152

AC:

670

ESP6500EA

AF:

0.0536

AC:

461

ExAC

AF:

0.125

AC:

15145

Asia WGS

AF:

0.298

AC:

1033

AN:

3478

EpiCase

AF:

0.0463

EpiControl

AF:

0.0453

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.60

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

.;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.014

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.73

T;T

MetaRNN

Benign

0.0057

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

2.0

.;M

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-8.0

D;D

REVEL

Benign

0.097

Sift

Pathogenic

0.0

D;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.13

MPC

0.77

ClinPred

0.053

GERP RS

2.5

Varity_R

0.16

gMVP

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over