Genetic Variant LNPK:c.707-1428delT (chr2-175941084-CA-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001305009.1(LNPK):c.707-5delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00138 in 374,596 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0023 ( 0 hom. )

Consequence

LNPK
NM_001305009.1 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.470

Publications

0 publications found

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]

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

LNPK links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001305009.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LNPK	NM_030650.3	MANE Select	c.707-1428delT	intron	N/A	NP_085153.1	Q9C0E8-1
LNPK	NM_001305008.1		c.905-1428delT	intron	N/A	NP_001291937.1	Q9C0E8
LNPK	NM_001305009.1		c.707-5delT	splice_region intron	N/A	NP_001291938.1	Q9C0E8-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LNPK	ENST00000272748.9	TSL:1 MANE Select	c.707-1428delT	intron	N/A	ENSP00000272748.4	Q9C0E8-1
LNPK	ENST00000544803.5	TSL:1	c.707-5delT	splice_region intron	N/A	ENSP00000440905.1	Q9C0E8-4
LNPK	ENST00000409660.5	TSL:1	c.338-1428delT	intron	N/A	ENSP00000386237.1	Q9C0E8-3

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

149684

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000245

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000201

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00666

AC:

271

AN:

40706

AF XY:

0.00685

show subpopulations

Gnomad AFR exome

AF:

0.0106

Gnomad AMR exome

AF:

0.00549

Gnomad ASJ exome

AF:

0.00739

Gnomad EAS exome

AF:

0.00734

Gnomad FIN exome

AF:

0.00682

Gnomad NFE exome

AF:

0.00717

Gnomad OTH exome

AF:

0.00246

GnomAD4 exome

AF:

0.00228

AC:

512

AN:

224828

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

294

AN XY:

129348

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00420

AC:

AN:

4288

American (AMR)

AF:

0.00340

AC:

AN:

14726

Ashkenazi Jewish (ASJ)

AF:

0.00352

AC:

AN:

7378

East Asian (EAS)

AF:

0.00377

AC:

AN:

6362

South Asian (SAS)

AF:

0.00158

AC:

AN:

46808

European-Finnish (FIN)

AF:

0.000777

AC:

AN:

10290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2194

European-Non Finnish (NFE)

AF:

0.00236

AC:

289

AN:

122344

Other (OTH)

AF:

0.00220

AC:

AN:

10438

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.241

Heterozygous variant carriers

172

259

345

431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000267

AC:

AN:

149768

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73084

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0000244

AC:

AN:

40930

American (AMR)

AF:

0.00

AC:

AN:

15054

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00

AC:

AN:

5092

South Asian (SAS)

AF:

0.00

AC:

AN:

4702

European-Finnish (FIN)

AF:

0.000201

AC:

AN:

9930

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67344

Other (OTH)

AF:

0.00

AC:

AN:

2072

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000000130562), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.263

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00414

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.47

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-175941084-CAA-CA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over