10-88820330-G-A

Variant names:

• chr10-88820330-G-A
• rs1473557485
• NM_001128215.1:c.1101G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001128215.1(LIPM):​c.1101G>A​(p.Met367Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,399,972 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: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: LIPM NM_001128215.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.20
• Publications: 0 publications found

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]

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.024849653).

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.1101G>A	p.Met367Ile	missense	Exon 9 of 9	NP_001121687.1	Q5VYY2-1
	ANKRD22	NM_144590.3	MANE Select	c.*2611C>T		3_prime_UTR	Exon 6 of 6	NP_653191.2	Q5VYY1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPM	ENST00000404743.9	TSL:1 MANE Select	c.1101G>A	p.Met367Ile	missense	Exon 9 of 9	ENSP00000383901.3	Q5VYY2-1
	ANKRD22	ENST00000371930.5	TSL:1 MANE Select	c.*2611C>T		3_prime_UTR	Exon 6 of 6	ENSP00000360998.4	Q5VYY1
	LIPM	ENST00000539337.2	TSL:2	c.981G>A	p.Met327Ile	missense	Exon 9 of 9	ENSP00000440375.1	Q5VYY2-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000640 AC: 1 AN: 156312 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000917

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1399972 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690458

African (AFR) AF: 0.00 AC: 0 AN: 31600

American (AMR) AF: 0.00 AC: 0 AN: 35710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.0000280 AC: 1 AN: 35740

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1079100

Other (OTH) AF: 0.00 AC: 0 AN: 58168

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.0020
DANN	Benign	0.77
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-1.4	N
PhyloP100		-4.2
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.089
Sift	Benign	0.41	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.029
MutPred		0.45		Loss of ubiquitination at K366 (P = 0.0634)
MVP		0.099
MPC		0.0020
ClinPred		0.048	T
GERP RS		-11
Varity_R		0.088
gMVP		0.29
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs1473557485; hg19: chr10-90580087;