chr1-160030590-T-C

Position:

chr1-160030590-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_145167.3(PIGM):c.1150A>G(p.Asn384Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 1,614,130 control chromosomes in the GnomAD database, including 730 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 329 hom., cov: 32)

Exomes 𝑓: 0.0081 ( 401 hom. )

Consequence

PIGM
NM_145167.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 7.29

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018675625).

BP6

Variant 1-160030590-T-C is Benign according to our data. Variant chr1-160030590-T-C is described in ClinVar as [Benign]. Clinvar id is 1166403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PIGM	NM_145167.3 linkuse as main transcript	c.1150A>G	p.Asn384Asp	missense_variant	1/1	ENST00000368090.5	NP_660150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PIGM	ENST00000368090.5 linkuse as main transcript	c.1150A>G	p.Asn384Asp	missense_variant	1/1		NM_145167.3	ENSP00000357069	P1

Frequencies

GnomAD3 genomes

AF:

0.0403

AC:

6138

AN:

152168

Hom.:

329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0214

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00316

Gnomad OTH

AF:

0.0316

GnomAD3 exomes

AF:

0.0162

AC:

4075

AN:

251446

Hom.:

173

AF XY:

0.0140

AC XY:

1906

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.137

Gnomad AMR exome

AF:

0.0133

Gnomad ASJ exome

AF:

0.0262

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0183

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00413

Gnomad OTH exome

AF:

0.0140

GnomAD4 exome

AF:

0.00810

AC:

11845

AN:

1461844

Hom.:

401

Cov.:

AF XY:

0.00810

AC XY:

5892

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.0141

Gnomad4 ASJ exome

AF:

0.0270

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0182

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00275

Gnomad4 OTH exome

AF:

0.0148

GnomAD4 genome

AF:

0.0403

AC:

6141

AN:

152286

Hom.:

329

Cov.:

AF XY:

0.0383

AC XY:

2856

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.0214

Gnomad4 ASJ

AF:

0.0294

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0180

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00316

Gnomad4 OTH

AF:

0.0313

Alfa

AF:

0.0120

Hom.:

144

Bravo

AF:

0.0462

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.129

AC:

567

ESP6500EA

AF:

0.00640

AC:

ExAC

AF:

0.0179

AC:

2171

Asia WGS

AF:

0.0160

AC:

AN:

3478

EpiCase

AF:

0.00594

EpiControl

AF:

0.00510

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 12, 2020	- -

PIGM-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 10, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hypercoagulability syndrome due to glycosylphosphatidylinositol deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 24, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.95

MutationAssessor

Benign

2.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.34

Sift

Benign

0.15

Sift4G

Benign

0.15

Polyphen

0.81

Vest4

0.30

MPC

1.0

ClinPred

0.036

GERP RS

5.3

Varity_R

0.57

gMVP

0.41

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