NM_030650.3:c.504G>A

Variant names:

• chr2-175947682-C-T
• rs2105565483
• NM_030650.3:c.504G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_030650.3(LNPK):​c.504G>A​(p.Gln168Gln) variant causes a synonymous 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LNPK NM_030650.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 2-175947682-C-T is Benign according to our data. Variant chr2-175947682-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1298842.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.13 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030650.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNPK	NM_030650.3	MANE Select	c.504G>A	p.Gln168Gln	synonymous	Exon 9 of 13	NP_085153.1	Q9C0E8-1
	LNPK	NM_001305008.1		c.702G>A	p.Gln234Gln	synonymous	Exon 9 of 13	NP_001291937.1	Q9C0E8
	LNPK	NM_001305009.1		c.504G>A	p.Gln168Gln	synonymous	Exon 9 of 14	NP_001291938.1	Q9C0E8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LNPK	ENST00000272748.9	TSL:1 MANE Select	c.504G>A	p.Gln168Gln	synonymous	Exon 9 of 13	ENSP00000272748.4	Q9C0E8-1
	LNPK	ENST00000544803.5	TSL:1	c.504G>A	p.Gln168Gln	synonymous	Exon 9 of 14	ENSP00000440905.1	Q9C0E8-4
	LNPK	ENST00000409660.5	TSL:1	c.135G>A	p.Gln45Gln	synonymous	Exon 7 of 11	ENSP00000386237.1	Q9C0E8-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000548

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.4
DANN	Benign	0.52
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2105565483; hg19: chr2-176812410;