1-160030645-A-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_145167.3(PIGM):c.1095T>A(p.Phe365Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 1,614,028 control chromosomes in the GnomAD database, including 24,426 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F365V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.13 ( 1635 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22791 hom. )

Consequence

PIGM
NM_145167.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.513

Variant links:

Genes affected

PIGM (HGNC:18858): (phosphatidylinositol glycan anchor biosynthesis class M) This gene encodes a transmembrane protein that is located in the endoplasmic reticulum and is involved in GPI-anchor biosynthesis. The glycosylphosphatidylinositol (GPI)-anchor is a glycolipid which contains three mannose molecules in its core backbone. The GPI-anchor is found on many blood cells and serves to anchor proteins to the cell surface. This gene encodes a mannosyltransferase, GPI-MT-I, that transfers the first mannose to GPI on the lumenal side of the endoplasmic reticulum. [provided by RefSeq, Jul 2008]

PIGM links:

KCNJ10 (HGNC:6256): (potassium inwardly rectifying channel subfamily J member 10) This gene encodes a member of the inward rectifier-type potassium channel family, characterized by having a greater tendency to allow potassium to flow into, rather than out of, a cell. The encoded protein may form a heterodimer with another potassium channel protein and may be responsible for the potassium buffering action of glial cells in the brain. Mutations in this gene have been associated with seizure susceptibility of common idiopathic generalized epilepsy syndromes. [provided by RefSeq, Jul 2008]

KCNJ10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019436479).

BP6

Variant 1-160030645-A-T is Benign according to our data. Variant chr1-160030645-A-T is described in ClinVar as [Benign]. Clinvar id is 1164402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PIGM	NM_145167.3 link	c.1095T>A	p.Phe365Leu	missense_variant	Exon 1 of 1	ENST00000368090.5	NP_660150.1	Q9H3S5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGM	ENST00000368090.5 link	c.1095T>A	p.Phe365Leu	missense_variant	Exon 1 of 1	6	NM_145167.3	ENSP00000357069.2		Q9H3S5

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

19372

AN:

152182

Hom.:

1635

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0325

Gnomad AMI

AF:

0.250

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.0375

Gnomad SAS

AF:

0.0980

Gnomad FIN

AF:

0.158

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.126

GnomAD2 exomes

AF:

0.144

AC:

36184

AN:

251442

AF XY:

0.144

show subpopulations

Gnomad AFR exome

AF:

0.0298

Gnomad AMR exome

AF:

0.166

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.0327

Gnomad FIN exome

AF:

0.157

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.170

AC:

249142

AN:

1461728

Hom.:

22791

Cov.:

AF XY:

0.169

AC XY:

122626

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0259

AC:

866

AN:

33480

Gnomad4 AMR exome

AF:

0.164

AC:

7340

AN:

44722

Gnomad4 ASJ exome

AF:

0.145

AC:

3791

AN:

26132

Gnomad4 EAS exome

AF:

0.0448

AC:

1779

AN:

39700

Gnomad4 SAS exome

AF:

0.102

AC:

8833

AN:

86252

Gnomad4 FIN exome

AF:

0.159

AC:

8520

AN:

53418

Gnomad4 NFE exome

AF:

0.187

AC:

208469

AN:

1111864

Gnomad4 Remaining exome

AF:

0.150

AC:

9038

AN:

60392

Heterozygous variant carriers

12780

25560

38341

51121

63901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

7106

14212

21318

28424

35530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.127

AC:

19379

AN:

152300

Hom.:

1635

Cov.:

AF XY:

0.125

AC XY:

9304

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0324

AC:

0.0323938

AN:

0.0323938

Gnomad4 AMR

AF:

0.137

AC:

0.137023

AN:

0.137023

Gnomad4 ASJ

AF:

0.141

AC:

0.141417

AN:

0.141417

Gnomad4 EAS

AF:

0.0372

AC:

0.0371583

AN:

0.0371583

Gnomad4 SAS

AF:

0.0972

AC:

0.0972222

AN:

0.0972222

Gnomad4 FIN

AF:

0.158

AC:

0.157989

AN:

0.157989

Gnomad4 NFE

AF:

0.185

AC:

0.185072

AN:

0.185072

Gnomad4 OTH

AF:

0.130

AC:

0.129858

AN:

0.129858

Heterozygous variant carriers

851

1701

2552

3402

4253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

216

432

648

864

1080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.171

Hom.:

1827

Bravo

AF:

0.120

TwinsUK

AF:

0.182

AC:

675

ALSPAC

AF:

0.192

AC:

740

ESP6500AA

AF:

0.0352

AC:

155

ESP6500EA

AF:

0.178

AC:

1528

ExAC

AF:

0.140

AC:

17052

Asia WGS

AF:

0.0850

AC:

296

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 27, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.7

DANN

Benign

0.90

DEOGEN2

Benign

0.013

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.1

REVEL

Benign

0.069

Sift

Benign

0.35

Sift4G

Benign

0.91

Polyphen

0.11

Vest4

0.092

MutPred

0.27

Loss of catalytic residue at F365 (P = 0.0226);

MPC

0.50

ClinPred

0.0053

GERP RS

-0.83

Varity_R

0.21

gMVP

0.34

Mutation Taster

=89/11

polymorphism (auto)

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over