10-88815461-C-G

Variant names:

• chr10-88815461-C-G
• NM_001128215.1:c.816C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001128215.1(LIPM):​c.816C>G​(p.Ile272Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,398,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LIPM NM_001128215.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.206

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20368674).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPM	NM_001128215.1	c.816C>G	p.Ile272Met	missense_variant	Exon 6 of 9	ENST00000404743.9	NP_001121687.1
LIPM	XM_011539748.4	c.816C>G	p.Ile272Met	missense_variant	Exon 6 of 9		XP_011538050.1
LIPM	XM_011539751.4	c.432C>G	p.Ile144Met	missense_variant	Exon 5 of 8		XP_011538053.1
LIPM	XM_011539752.4	c.246C>G	p.Ile82Met	missense_variant	Exon 4 of 7		XP_011538054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPM	ENST00000404743.9	c.816C>G	p.Ile272Met	missense_variant	Exon 6 of 9	1	NM_001128215.1	ENSP00000383901.3
LIPM	ENST00000539337.2	c.696C>G	p.Ile232Met	missense_variant	Exon 6 of 9	2		ENSP00000440375.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000214 AC: 3 AN: 1398978 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690018

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: 0.00

Gnomad4 NFE exome AF: 0.00000278

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.816C>G (p.I272M) alteration is located in exon 6 (coding exon 6) of the LIPM gene. This alteration results from a C to G substitution at nucleotide position 816, causing the isoleucine (I) at amino acid position 272 to be replaced by a methionine (M). 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	0.081
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0067	T;.
Eigen	Benign	0.076
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.20	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.5	L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.87	N;N
REVEL	Benign	0.12
Sift	Benign	0.047	D;T
Sift4G	Benign	0.15	T;T
Polyphen		0.75	P;.
Vest4		0.28
MutPred		0.49		Loss of stability (P = 0.3258);.;
MVP		0.46
MPC		0.0040
ClinPred		0.64	D
GERP RS		4.8
Varity_R		0.17
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: chr10-90575218;