5-97124534-G-A

Variant names:

• chr5-97124534-G-A
• NM_153234.5:c.178C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153234.5(LIX1):​c.178C>T​(p.Pro60Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign 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: 3.62
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3119022).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIX1	NM_153234.5	c.178C>T	p.Pro60Ser	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.178C>T	p.Pro60Ser	missense_variant	Exon 2 of 6	1	NM_153234.5	ENSP00000274382.4
LIX1	ENST00000512378.1	c.106C>T	p.Pro36Ser	missense_variant	Exon 3 of 4	5		ENSP00000427469.1
LIX1-AS1	ENST00000504578.2	n.573+21440G>A		intron_variant	Intron 3 of 6	5

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

Jun 10, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.178C>T (p.P60S) alteration is located in exon 2 (coding exon 2) of the LIX1 gene. This alteration results from a C to T substitution at nucleotide position 178, causing the proline (P) at amino acid position 60 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	0.091
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T;.
Eigen	Benign	0.0098
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.31	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
PhyloP100		3.6
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-5.8	D;D
REVEL	Benign	0.12
Sift	Benign	0.055	T;T
Sift4G	Benign	0.097	T;.
Polyphen		0.0050	B;.
Vest4		0.39
MutPred		0.41		Loss of catalytic residue at P60 (P = 0.0668);.;
MVP		0.44
MPC		0.21
ClinPred		0.97	D
GERP RS		5.5
Varity_R		0.22
gMVP		0.52
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr5-96460238;