chr2-175941013-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001305009.1(LNPK):​c.774G>A​(p.Ser258Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000998 in 453,078 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00084 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

LNPK
NM_001305009.1 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.36
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.97).
BP6
Variant 2-175941013-C-T is Benign according to our data. Variant chr2-175941013-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651553.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.36 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000836 (127/151914) while in subpopulation NFE AF= 0.000913 (62/67944). AF 95% confidence interval is 0.00073. There are 0 homozygotes in gnomad4. There are 58 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LNPKNM_030650.3 linkc.707-1356G>A intron_variant Intron 9 of 12 ENST00000272748.9 NP_085153.1 Q9C0E8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LNPKENST00000544803.5 linkc.774G>A p.Ser258Ser synonymous_variant Exon 10 of 14 1 ENSP00000440905.1 Q9C0E8-4
LNPKENST00000272748.9 linkc.707-1356G>A intron_variant Intron 9 of 12 1 NM_030650.3 ENSP00000272748.4 Q9C0E8-1
LNPKENST00000409660.5 linkc.338-1356G>A intron_variant Intron 7 of 10 1 ENSP00000386237.1 Q9C0E8-3
LNPKENST00000431754.1 linkn.32-1356G>A intron_variant Intron 1 of 3 5 ENSP00000388507.1 H7BZA1

Frequencies

GnomAD3 genomes
AF:
0.000837
AC:
127
AN:
151794
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000329
Gnomad ASJ
AF:
0.0144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000912
Gnomad OTH
AF:
0.00240
GnomAD3 exomes
AF:
0.00147
AC:
184
AN:
125036
Hom.:
2
AF XY:
0.00147
AC XY:
101
AN XY:
68580
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000334
Gnomad ASJ exome
AF:
0.0159
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000452
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000935
Gnomad OTH exome
AF:
0.00128
GnomAD4 exome
AF:
0.00108
AC:
325
AN:
301164
Hom.:
2
Cov.:
0
AF XY:
0.000990
AC XY:
170
AN XY:
171694
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000334
Gnomad4 ASJ exome
AF:
0.0153
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000793
Gnomad4 OTH exome
AF:
0.00192
GnomAD4 genome
AF:
0.000836
AC:
127
AN:
151914
Hom.:
0
Cov.:
31
AF XY:
0.000781
AC XY:
58
AN XY:
74252
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.000328
Gnomad4 ASJ
AF:
0.0144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000913
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00273
Hom.:
0
Bravo
AF:
0.000918
Asia WGS
AF:
0.000289
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Aug 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

LNPK: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.97
CADD
Benign
0.40
DANN
Benign
0.39

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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.

Other links and lift over

dbSNP: rs760528892; hg19: chr2-176805741; API