5-97094835-T-A

Position:

• chr5-97094835-T-A

Variant summary

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

The NM_153234.5(LIX1):​c.762A>T​(p.Leu254Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIX1 NM_153234.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0600

Genes affected

LIX1 (HGNC:18581): (limb and CNS expressed 1) Predicted to be involved in autophagosome maturation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LIX1-AS1 (HGNC:):

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	Protein	UniProt
LIX1	NM_153234.5	c.762A>T	p.Leu254Phe	missense_variant	6/6	ENST00000274382.9	NP_694966.3
LIX1-AS1	NR_187470.1	n.345-4102T>A		intron_variant
LIX1-AS1	NR_187471.1	n.226-6924T>A		intron_variant
LIX1-AS1	NR_187472.1	n.115-4102T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIX1	ENST00000274382.9	c.762A>T	p.Leu254Phe	missense_variant	6/6	1	NM_153234.5	ENSP00000274382.4
LIX1-AS1	ENST00000504578.2	n.130+5631T>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000712 Hom.: 0

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

Nov 08, 2024

The c.762A>T (p.L254F) alteration is located in exon 6 (coding exon 6) of the LIX1 gene. This alteration results from a A to T substitution at nucleotide position 762, causing the leucine (L) at amino acid position 254 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	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.34	T
Eigen	Benign	0.19
Eigen_PC	Benign	0.12
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.56	D
MetaSVM	Benign	-0.63	T
MutationAssessor	Benign	2.0	M
PrimateAI	Uncertain	0.62	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.39		Gain of methylation at K249 (P = 0.0652);
MVP		0.53
MPC		0.81
ClinPred		0.98	D
GERP RS		1.5
Varity_R		0.52
gMVP		0.49

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

LitVar

Other links and lift over

dbSNP: rs1241774603; hg19: chr5-96430539;