Genetic Variant LIPM:p.Asn401Lys (chr10-88820432-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001128215.1(LIPM):c.1203T>A(p.Asn401Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000015 in 1,399,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

LIPM
NM_001128215.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.235

Publications

0 publications found

Variant links:

Genes affected

LIPM (HGNC:23455): (lipase family member M) Predicted to enable lipoprotein lipase activity. Predicted to be involved in cornification. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

LIPM links:

ANKRD22 (HGNC:28321): (ankyrin repeat domain 22)

ANKRD22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12814853).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128215.1. 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
	LIPM	NM_001128215.1	MANE Select	c.1203T>A	p.Asn401Lys	missense	Exon 9 of 9	NP_001121687.1	Q5VYY2-1
	ANKRD22	NM_144590.3	MANE Select	c.*2509A>T		3_prime_UTR	Exon 6 of 6	NP_653191.2	Q5VYY1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
LIPM	ENST00000404743.9	TSL:1 MANE Select	c.1203T>A	p.Asn401Lys	missense	Exon 9 of 9	ENSP00000383901.3	Q5VYY2-1
ANKRD22	ENST00000371930.5	TSL:1 MANE Select	c.*2509A>T		3_prime_UTR	Exon 6 of 6	ENSP00000360998.4	Q5VYY1
LIPM	ENST00000539337.2	TSL:2	c.1083T>A	p.Asn361Lys	missense	Exon 9 of 9	ENSP00000440375.1	Q5VYY2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000637

AC:

AN:

157082

AF XY:

0.0000120

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000166

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000150

AC:

AN:

1399836

Hom.:

Cov.:

AF XY:

0.0000159

AC XY:

AN XY:

690402

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.00

AC:

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.00

AC:

AN:

79234

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49482

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0000195

AC:

AN:

1079050

Other (OTH)

AF:

0.00

AC:

AN:

58148

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

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

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.026

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.11

M_CAP

Benign

0.018

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.93

PhyloP100

-0.23

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.2

REVEL

Benign

0.079

Sift

Benign

0.21

Sift4G

Benign

0.83

Polyphen

0.0070

Vest4

0.18

MutPred

0.50

Gain of methylation at N401 (P = 0.0032)

MVP

0.74

MPC

0.0020

ClinPred

0.074

GERP RS

2.1

Varity_R

0.092

gMVP

0.74

Mutation Taster

=88/12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over