Variant chr2-175964389-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000272748.9(LNPK):c.476C>G(p.Thr159Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0501 in 1,612,372 control chromosomes in the GnomAD database, including 2,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.036 ( 154 hom., cov: 32)

Exomes 𝑓: 0.051 ( 2283 hom. )

Consequence

LNPK
ENST00000272748.9 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 5.21

Variant links:

Genes affected

LNPK (HGNC:21610): (lunapark, ER junction formation factor) Enables identical protein binding activity. Involved in endoplasmic reticulum tubular network maintenance and positive regulation of endoplasmic reticulum tubular network organization. Located in endoplasmic reticulum tubular network membrane and nucleoplasm. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

LNPK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0032927692).

BP6

Variant 2-175964389-G-C is Benign according to our data. Variant chr2-175964389-G-C is described in ClinVar as [Benign]. Clinvar id is 3056923.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LNPK	NM_030650.3 linkuse as main transcript	c.476C>G	p.Thr159Ser	missense_variant	8/13	ENST00000272748.9	NP_085153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LNPK	ENST00000272748.9 linkuse as main transcript	c.476C>G	p.Thr159Ser	missense_variant	8/13	1	NM_030650.3	ENSP00000272748	P1	Q9C0E8-1
LNPK	ENST00000544803.5 linkuse as main transcript	c.476C>G	p.Thr159Ser	missense_variant	8/14	1		ENSP00000440905		Q9C0E8-4
LNPK	ENST00000409660.5 linkuse as main transcript	c.107C>G	p.Thr36Ser	missense_variant	6/11	1		ENSP00000386237		Q9C0E8-3

Frequencies

GnomAD3 genomes

AF:

0.0364

AC:

5540

AN:

152118

Hom.:

154

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0112

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0265

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0201

Gnomad FIN

AF:

0.0272

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0603

Gnomad OTH

AF:

0.0335

GnomAD3 exomes

AF:

0.0350

AC:

8793

AN:

251078

Hom.:

223

AF XY:

0.0356

AC XY:

4835

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.0109

Gnomad AMR exome

AF:

0.0163

Gnomad ASJ exome

AF:

0.0181

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0212

Gnomad FIN exome

AF:

0.0268

Gnomad NFE exome

AF:

0.0562

Gnomad OTH exome

AF:

0.0431

GnomAD4 exome

AF:

0.0515

AC:

75190

AN:

1460136

Hom.:

2283

Cov.:

AF XY:

0.0508

AC XY:

36911

AN XY:

726482

show subpopulations

Gnomad4 AFR exome

AF:

0.00867

Gnomad4 AMR exome

AF:

0.0173

Gnomad4 ASJ exome

AF:

0.0198

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0208

Gnomad4 FIN exome

AF:

0.0302

Gnomad4 NFE exome

AF:

0.0605

Gnomad4 OTH exome

AF:

0.0470

GnomAD4 genome

AF:

0.0364

AC:

5542

AN:

152236

Hom.:

154

Cov.:

AF XY:

0.0331

AC XY:

2464

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0112

Gnomad4 AMR

AF:

0.0265

Gnomad4 ASJ

AF:

0.0236

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0205

Gnomad4 FIN

AF:

0.0272

Gnomad4 NFE

AF:

0.0603

Gnomad4 OTH

AF:

0.0331

Alfa

AF:

0.0521

Hom.:

200

Bravo

AF:

0.0340

TwinsUK

AF:

0.0577

AC:

214

ALSPAC

AF:

0.0695

AC:

268

ESP6500AA

AF:

0.0145

AC:

ESP6500EA

AF:

0.0610

AC:

525

ExAC

AF:

0.0360

AC:

4369

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0565

EpiControl

AF:

0.0506

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

LNPK-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 27, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

T;.;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.45

T;T;T

MetaRNN

Benign

0.0033

T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.9

L;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-2.2

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.073

T;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.65

P;.;.

Vest4

0.29

MutPred

0.17

Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;

MPC

0.12

ClinPred

0.037

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.27

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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