chr1-145942735-G-C

Position:

• chr1-145942735-G-C

Variant summary

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

The ENST00000604000.4(LIX1L):​c.575C>G​(p.Ser192Cys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIX1L ENST00000604000.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.83

Genes affected

LIX1L (HGNC:28715): (limb and CNS expressed 1 like) Predicted to be involved in autophagosome maturation. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000280778 (HGNC:):

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=0.18816924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIX1L	NM_153713.3	c.575C>G	p.Ser192Cys	missense_variant	3/6	ENST00000604000.4	NP_714924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIX1L	ENST00000604000.4	c.575C>G	p.Ser192Cys	missense_variant	3/6	1	NM_153713.3	ENSP00000474487.3
ENSG00000280778	ENST00000625258.1	c.-30+15446G>C		intron_variant		5		ENSP00000487094.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Mar 22, 2023

The c.575C>G (p.S192C) alteration is located in exon 3 (coding exon 3) of the LIX1L gene. This alteration results from a C to G substitution at nucleotide position 575, causing the serine (S) at amino acid position 192 to be replaced by a cysteine (C). 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	0.083
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	23
DANN	Benign	0.87
DEOGEN2	Benign	0.073	T
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.19	T
Sift4G	Benign	0.072	T
Vest4		0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.67

Splicing

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: chr1-145492353;