chr1-145957668-C-T

Position:

• chr1-145957668-C-T

Variant summary

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

The ENST00000604000.4(LIX1L):​c.260G>A​(p.Ser87Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000216 in 1,389,366 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: LIX1L ENST00000604000.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.77

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIX1L	NM_153713.3	c.260G>A	p.Ser87Asn	missense_variant	1/6	ENST00000604000.4	NP_714924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIX1L	ENST00000604000.4	c.260G>A	p.Ser87Asn	missense_variant	1/6	1	NM_153713.3	ENSP00000474487.3
ENSG00000280778	ENST00000625258.1	c.-29-19416C>T		intron_variant		5		ENSP00000487094.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000190 AC: 3 AN: 158192 Hom.: 0 AF XY: 0.0000334 AC XY: 3 AN XY: 89910

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000433

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000216 AC: 3 AN: 1389366 Hom.: 0 Cov.: 32 AF XY: 0.00000435 AC XY: 3 AN XY: 690262

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000277

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000378

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

Jul 06, 2021

The c.260G>A (p.S87N) alteration is located in exon 1 (coding exon 1) of the LIX1L gene. This alteration results from a G to A substitution at nucleotide position 260, causing the serine (S) at amino acid position 87 to be replaced by an asparagine (N). 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	0.98
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.087	T
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.27	T
Sift4G	Uncertain	0.030	D
Vest4		0.33
gMVP		0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.87		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.87		Position offset: -6

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

Publications

LitVar

Other links and lift over

dbSNP: rs782319037; hg19: chr1-145477418;