5-97124507-A-C

Position:

• chr5-97124507-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_153234.5(LIX1):​c.205T>G​(p.Tyr69Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIX1 NM_153234.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.04

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:52976): (LIX1 and RIOK2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.841

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIX1	NM_153234.5	c.205T>G	p.Tyr69Asp	missense_variant	2/6	ENST00000274382.9	NP_694966.3
LIX1-AS1	XR_007058883.1	n.4604+21413A>C		intron_variant, non_coding_transcript_variant
LIX1-AS1	XR_948603.3	n.4605-6589A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIX1	ENST00000274382.9	c.205T>G	p.Tyr69Asp	missense_variant	2/6	1	NM_153234.5	ENSP00000274382	P1
LIX1-AS1	ENST00000504578.2	n.573+21413A>C		intron_variant, non_coding_transcript_variant		5
LIX1	ENST00000512378.1	c.133T>G	p.Tyr45Asp	missense_variant	3/4	5		ENSP00000427469

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Dec 20, 2023

The c.205T>G (p.Y69D) alteration is located in exon 2 (coding exon 2) of the LIX1 gene. This alteration results from a T to G substitution at nucleotide position 205, causing the tyrosine (Y) at amino acid position 69 to be replaced by an aspartic acid (D). 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	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Uncertain	2.2	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Pathogenic	-7.2	D;D
REVEL	Pathogenic	0.78
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;.
Polyphen		1.0	D;.
Vest4		0.91
MutPred		0.64		Gain of disorder (P = 0.0153);.;
MVP		0.89
MPC		1.0
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.92
gMVP		0.88

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: chr5-96460211;