chr5-97107364-G-T

Variant names:

• chr5-97107364-G-T
• rs1747105550
• NM_153234.5:c.383C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153234.5(LIX1):​c.383C>A​(p.Thr128Asn) 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T128I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIX1 NM_153234.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17132491).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIX1	NM_153234.5	c.383C>A	p.Thr128Asn	missense_variant	Exon 3 of 6	ENST00000274382.9	NP_694966.3
LIX1-AS1	NR_187470.1	n.824+4270G>T		intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIX1	ENST00000274382.9	c.383C>A	p.Thr128Asn	missense_variant	Exon 3 of 6	1	NM_153234.5	ENSP00000274382.4
LIX1-AS1	ENST00000504578.2	n.573+4270G>T		intron_variant	Intron 3 of 6	5
LIX1	ENST00000512378.1	c.*120C>A		downstream_gene_variant		5		ENSP00000427469.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	L
PhyloP100		3.8
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.079
Sift	Benign	0.11	T
Sift4G	Benign	0.17	T
Polyphen		0.14	B
Vest4		0.39
MutPred		0.20		Loss of glycosylation at T128 (P = 0.0504);
MVP		0.37
MPC		0.34
ClinPred		0.61	D
GERP RS		5.2
Varity_R		0.087
gMVP		0.44
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

dbSNP: rs1747105550; hg19: chr5-96443068;