10-88740012-A-T

Variant names:

• chr10-88740012-A-T
• NM_001080518.2:c.833A>T

Variant summary

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

The NM_001080518.2(LIPK):​c.833A>T​(p.Tyr278Phe) variant causes a missense change. 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)
  • Exomes 𝑓: 0.000058 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LIPK NM_001080518.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.52

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPK	NM_001080518.2	c.833A>T	p.Tyr278Phe	missense_variant	Exon 8 of 10	ENST00000404190.3	NP_001073987.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPK	ENST00000404190.3	c.833A>T	p.Tyr278Phe	missense_variant	Exon 8 of 10	1	NM_001080518.2	ENSP00000383900.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000581 AC: 82 AN: 1410728 Hom.: 0 Cov.: 29 AF XY: 0.0000583 AC XY: 41 AN XY: 703236

Gnomad4 AFR exome AF: 0.0000624

Gnomad4 AMR exome AF: 0.0000457

Gnomad4 ASJ exome AF: 0.0000817

Gnomad4 EAS exome AF: 0.0000546

Gnomad4 SAS exome AF: 0.0000117

Gnomad4 FIN exome AF: 0.0000607

Gnomad4 NFE exome AF: 0.0000604

Gnomad4 OTH exome AF: 0.0000874

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 15, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.833A>T (p.Y278F) alteration is located in exon 7 (coding exon 7) of the LIPK gene. This alteration results from a A to T substitution at nucleotide position 833, causing the tyrosine (Y) at amino acid position 278 to be replaced by a phenylalanine (F). 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	0.17
BayesDel_addAF	Benign	-0.024	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.63	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.41
Sift	Benign	0.035	D
Sift4G	Benign	0.12	T
Polyphen		0.98	D
Vest4		0.51
MutPred		0.62		Loss of phosphorylation at Y278 (P = 0.0405);
MVP		0.75
MPC		0.025
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.30
gMVP		0.72

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: chr10-90499769;