1-145957650-T-C

Position:

• chr1-145957650-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_153713.3(LIX1L):​c.278A>G​(p.Gln93Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,389,446 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: 0.0000014 (0 hom.)
• Consequence: LIX1L NM_153713.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.86

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]

LIX1L-AS1 (HGNC:41210): (LIX1L antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30146518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIX1L	NM_153713.3	c.278A>G	p.Gln93Arg	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.278A>G	p.Gln93Arg	missense_variant	1/6	1	NM_153713.3	ENSP00000474487	P1
LIX1L-AS1	ENST00000630257.2	n.652-1357T>C		intron_variant, non_coding_transcript_variant		5
LIX1L-AS1	ENST00000600340.5	n.515-711T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1389446 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690628

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000565

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Sep 15, 2021

The c.278A>G (p.Q93R) alteration is located in exon 1 (coding exon 1) of the LIX1L gene. This alteration results from a A to G substitution at nucleotide position 278, causing the glutamine (Q) at amino acid position 93 to be replaced by an arginine (R). 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	Uncertain	0.53
BayesDel_noAF	Benign	-0.31
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.073	T
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.30	T
Sift4G	Benign	0.43	T
Vest4		0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
gMVP		0.78

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: rs782786458; hg19: chr1-145477436;