10-88724634-G-A

Position:

• chr10-88724634-G-A

Variant summary

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

The NM_001080518.2(LIPK):​c.91G>A​(p.Ala31Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LIPK NM_001080518.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.67

Genes affected

LIPK (HGNC:23444): (lipase family member K) Predicted to enable lipoprotein lipase activity. Predicted to be involved in cornification. Predicted to be located in extracellular region. Predicted to be active in intracellular membrane-bounded organelle. [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=0.21564555).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPK	NM_001080518.2	c.91G>A	p.Ala31Thr	missense_variant	2/10	ENST00000404190.3	NP_001073987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPK	ENST00000404190.3	c.91G>A	p.Ala31Thr	missense_variant	2/10	1	NM_001080518.2	ENSP00000383900	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442494 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 717086

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: 9.06e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

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 03, 2022

The c.91G>A (p.A31T) alteration is located in exon 1 (coding exon 1) of the LIPK gene. This alteration results from a G to A substitution at nucleotide position 91, causing the alanine (A) at amino acid position 31 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	Benign	0.11
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0022	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.94	N
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.18
Sift	Benign	0.27	T
Sift4G	Benign	0.32	T
Polyphen		0.87	P
Vest4		0.18
MutPred		0.60		Gain of helix (P = 0.1736);
MVP		0.76
MPC		0.018
ClinPred		0.90	D
GERP RS		4.8
Varity_R		0.078
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs1260434550; hg19: chr10-90484391;