2-175937467-T-C

Position:

• chr2-175937467-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030650.3(LNPK):​c.931A>G​(p.Arg311Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LNPK NM_030650.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.45

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3998667).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LNPK	NM_030650.3	c.931A>G	p.Arg311Gly	missense_variant	12/13	ENST00000272748.9	NP_085153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LNPK	ENST00000272748.9	c.931A>G	p.Arg311Gly	missense_variant	12/13	1	NM_030650.3	ENSP00000272748.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Nov 21, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	26
DANN	Benign	0.93
DEOGEN2	Uncertain	0.77	D;.;.
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.075	D
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.2	M;.;.
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-6.4	D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;.;.
Vest4		0.59
MutPred		0.30		Gain of ubiquitination at K309 (P = 0.0417);.;.;
MVP		0.72
MPC		0.69
ClinPred		0.98	D
GERP RS		5.6
Varity_R		0.78
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-176802195;