2-175964389-G-C

Variant names:

• chr2-175964389-G-C
• rs34897061
• NM_030650.3:c.476C>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_030650.3(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 NM_030650.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 5.21

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]

ACMG classification

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 rank	MANE	Protein	UniProt
LNPK	NM_030650.3	c.476C>G	p.Thr159Ser	missense_variant	Exon 8 of 13	ENST00000272748.9	NP_085153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LNPK	ENST00000272748.9	c.476C>G	p.Thr159Ser	missense_variant	Exon 8 of 13	1	NM_030650.3	ENSP00000272748.4
LNPK	ENST00000544803.5	c.476C>G	p.Thr159Ser	missense_variant	Exon 8 of 14	1		ENSP00000440905.1
LNPK	ENST00000409660.5	c.107C>G	p.Thr36Ser	missense_variant	Exon 6 of 11	1		ENSP00000386237.1

Frequencies

GnomAD3 genomes AF: 0.0364 AC: 5540 AN: 152118 Hom.: 154 Cov.: 32

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

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.: 30 AF XY: 0.0508 AC XY: 36911 AN XY: 726482

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.: 32 AF XY: 0.0331 AC XY: 2464 AN XY: 74426

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: 64

ESP6500EA AF: 0.0610 AC: 525

ExAC AF: 0.0360 AC: 4369

Asia WGS AF: 0.0130 AC: 44 AN: 3478

EpiCase AF: 0.0565

EpiControl AF: 0.0506

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

LNPK-related disorder Benign:1

Apr 27, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;.;.
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.45	T;T;T
MetaRNN	Benign	0.0033	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L;L;.
PrimateAI	Uncertain	0.50	T
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	T
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

Other links and lift over

dbSNP: rs34897061; hg19: chr2-176829117;