chr10-88820425-T-C

Position:

• chr10-88820425-T-C

Variant summary

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

The NM_001128215.1(LIPM):​c.1196T>C​(p.Met399Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIPM NM_001128215.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.68

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPM	NM_001128215.1	c.1196T>C	p.Met399Thr	missense_variant	9/9	ENST00000404743.9
ANKRD22	NM_144590.3	c.*2516A>G		3_prime_UTR_variant	6/6	ENST00000371930.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPM	ENST00000404743.9	c.1196T>C	p.Met399Thr	missense_variant	9/9	1	NM_001128215.1	P1
ANKRD22	ENST00000371930.5	c.*2516A>G		3_prime_UTR_variant	6/6	1	NM_144590.3	P1
LIPM	ENST00000539337.2	c.1076T>C	p.Met359Thr	missense_variant	9/9	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2024

The c.1196T>C (p.M399T) alteration is located in exon 9 (coding exon 9) of the LIPM gene. This alteration results from a T to C substitution at nucleotide position 1196, causing the methionine (M) at amino acid position 399 to be replaced by a threonine (T). 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	Uncertain	0.52
BayesDel_addAF	Benign	-0.0091	T
BayesDel_noAF	Benign	-0.25
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.076	T;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.84	T;T
M_CAP	Benign	0.068	D
MetaRNN	Uncertain	0.53	D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	0.81	D;D
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Uncertain	0.40
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.28	B;.
Vest4		0.31
MutPred		0.79		Gain of phosphorylation at M399 (P = 0.059);.;
MVP		0.75
MPC		0.0028
ClinPred		0.92	D
GERP RS		5.8
Varity_R		0.73
gMVP		0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-90580182;