5-97124576-C-A

Variant names:

• chr5-97124576-C-A
• rs1747866428
• NM_153234.5:c.136G>T

Variant summary

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

The NM_153234.5(LIX1):​c.136G>T​(p.Ala46Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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: 1.98

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09108046).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIX1	NM_153234.5	c.136G>T	p.Ala46Ser	missense_variant	Exon 2 of 6	ENST00000274382.9	NP_694966.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIX1	ENST00000274382.9	c.136G>T	p.Ala46Ser	missense_variant	Exon 2 of 6	1	NM_153234.5	ENSP00000274382.4
LIX1	ENST00000512378.1	c.64G>T	p.Ala22Ser	missense_variant	Exon 3 of 4	5		ENSP00000427469.1
LIX1-AS1	ENST00000504578.2	n.573+21482C>A		intron_variant	Intron 3 of 6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.136G>T (p.A46S) alteration is located in exon 2 (coding exon 2) of the LIX1 gene. This alteration results from a G to T substitution at nucleotide position 136, causing the alanine (A) at amino acid position 46 to be replaced by a serine (S). 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	0.082
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.87
DEOGEN2	Benign	0.061	T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.091	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.95	L;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.015
Sift	Benign	0.081	T;T
Sift4G	Benign	0.28	T;.
Polyphen		0.14	B;.
Vest4		0.50
MutPred		0.21		Gain of disorder (P = 0.03);.;
MVP		0.29
MPC		0.19
ClinPred		0.12	T
GERP RS		1.4
Varity_R		0.029
gMVP		0.23

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: rs1747866428; hg19: chr5-96460280;