rs749598231

Variant names:

• chr2-175964387-C-G
• NM_030650.3:c.478G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-175964387-C-G
• chr2-175964387-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030650.3(LNPK):​c.478G>C​(p.Ala160Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,460,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A160T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LNPK NM_030650.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.135

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04578969).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LNPK	NM_030650.3	c.478G>C	p.Ala160Pro	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.478G>C	p.Ala160Pro	missense_variant	Exon 8 of 13	1	NM_030650.3	ENSP00000272748.4
LNPK	ENST00000544803.5	c.478G>C	p.Ala160Pro	missense_variant	Exon 8 of 14	1		ENSP00000440905.1
LNPK	ENST00000409660.5	c.109G>C	p.Ala37Pro	missense_variant	Exon 6 of 11	1		ENSP00000386237.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1460942 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726836

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.76
DEOGEN2	Benign	0.12	T;.;.
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.31	N
LIST_S2	Uncertain	0.87	D;T;D
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.046	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.3	N;N;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	2.7	N;N;N
REVEL	Benign	0.12
Sift	Benign	1.0	T;T;T
Sift4G	Benign	1.0	T;T;T
Polyphen		0.0	B;.;.
Vest4		0.14
MutPred		0.19		Loss of MoRF binding (P = 0.0617);Loss of MoRF binding (P = 0.0617);.;
MVP		0.33
MPC		0.17
ClinPred		0.28	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.26

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-176829115;