8-142841204-C-T

Variant names:

• chr8-142841204-C-T
• rs3764795
• NM_002066.3:c.160C>T

Variant summary

Our verdict is Benign. The variant received -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.

• Frequency:
  • Genomes: 𝑓 0.11 (1519 hom., cov: 33)
  • Exomes 𝑓: 0.075 (8434 hom.)
• Consequence: GML NM_002066.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663
• Publications: 18 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

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.160C>T	p.Arg54Cys	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.160C>T	p.Arg54Cys	missense	Exon 3 of 4	ENSP00000220940.1	Q99445
	GML	ENST00000522728.5	TSL:3	c.160C>T	p.Arg54Cys	missense	Exon 3 of 5	ENSP00000430799.1	E5RI31

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16819 AN: 152042 Hom.: 1512 Cov.: 33

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

GnomAD2 exomes AF: 0.127 AC: 31898 AN: 251266 AF XY: 0.124

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 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.: 23 AF XY: 0.0789 AC XY: 53622 AN XY: 679892

African (AFR) AF: 0.147 AC: 4562 AN: 31048

American (AMR) AF: 0.153 AC: 6815 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.0835 AC: 2120 AN: 25384

East Asian (EAS) AF: 0.463 AC: 18004 AN: 38878

South Asian (SAS) AF: 0.180 AC: 15065 AN: 83782

European-Finnish (FIN) AF: 0.0898 AC: 4791 AN: 53378

Middle Eastern (MID) AF: 0.0716 AC: 397 AN: 5546

European-Non Finnish (NFE) AF: 0.0448 AC: 45446 AN: 1015504

Other (OTH) AF: 0.0890 AC: 5053 AN: 56748

GnomAD4 genome AF: 0.111 AC: 16851 AN: 152162 Hom.: 1519 Cov.: 33 AF XY: 0.116 AC XY: 8647 AN XY: 74394

African (AFR) AF: 0.151 AC: 6253 AN: 41504

American (AMR) AF: 0.131 AC: 2002 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0983 AC: 341 AN: 3468

East Asian (EAS) AF: 0.480 AC: 2478 AN: 5162

South Asian (SAS) AF: 0.189 AC: 911 AN: 4814

European-Finnish (FIN) AF: 0.0800 AC: 849 AN: 10606

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0551 AC: 3746 AN: 68002

Other (OTH) AF: 0.102 AC: 216 AN: 2110

Alfa AF: 0.0774 Hom.: 2898

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.014
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.66
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-8.0	D
REVEL	Benign	0.097
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.13
MPC		0.77
ClinPred		0.053	T
GERP RS		2.5
Varity_R		0.16
gMVP		0.57
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3764795; hg19: chr8-143922620; COSMIC: COSV55277278;