Variant 10-88820479-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001128215.1(LIPM):c.1250G>C(p.Gly417Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000124 in 1,551,110 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

LIPM
NM_001128215.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0140

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 made for transcript

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=0.032938033).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPM	NM_001128215.1 linkuse as main transcript	c.1250G>C	p.Gly417Ala	missense_variant	9/9	ENST00000404743.9
ANKRD22	NM_144590.3 linkuse as main transcript	c.*2462C>G		3_prime_UTR_variant	6/6	ENST00000371930.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPM	ENST00000404743.9 linkuse as main transcript	c.1250G>C	p.Gly417Ala	missense_variant	9/9	1	NM_001128215.1	P1	Q5VYY2-1
ANKRD22	ENST00000371930.5 linkuse as main transcript	c.*2462C>G		3_prime_UTR_variant	6/6	1	NM_144590.3	P1
LIPM	ENST00000539337.2 linkuse as main transcript	c.1130G>C	p.Gly377Ala	missense_variant	9/9	2			Q5VYY2-2

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000109

AC:

AN:

156468

Hom.:

AF XY:

0.000157

AC XY:

AN XY:

82888

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000725

Gnomad NFE exome

AF:

0.0000660

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

AF:

0.000119

AC:

166

AN:

1398942

Hom.:

Cov.:

AF XY:

0.000125

AC XY:

AN XY:

690002

show subpopulations

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:

0.00

Gnomad4 FIN exome

AF:

0.000673

Gnomad4 NFE exome

AF:

0.000120

Gnomad4 OTH exome

AF:

0.0000690

GnomAD4 genome

AF:

0.000171

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00113

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.0000775

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

The c.1250G>C (p.G417A) alteration is located in exon 9 (coding exon 9) of the LIPM gene. This alteration results from a G to C substitution at nucleotide position 1250, causing the glycine (G) at amino acid position 417 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.6

DANN

Benign

0.79

DEOGEN2

Benign

0.0016

T;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.052

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.37

N;N

REVEL

Benign

0.12

Sift

Benign

0.032

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.0010

B;.

Vest4

0.092

MVP

0.58

MPC

0.0023

ClinPred

0.10

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.055

gMVP

0.50

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over