chr5-97094978-C-T

Variant names:

• chr5-97094978-C-T
• rs2112743524
• NM_153234.5:c.619G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_153234.5(LIX1):​c.619G>A​(p.Ala207Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LIX1 NM_153234.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.83
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.751

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153234.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIX1	NM_153234.5	MANE Select	c.619G>A	p.Ala207Thr	missense	Exon 6 of 6	NP_694966.3
	LIX1-AS1	NR_187470.1		n.345-3959C>T		intron	N/A
	LIX1-AS1	NR_187471.1		n.226-6781C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIX1	ENST00000274382.9	TSL:1 MANE Select	c.619G>A	p.Ala207Thr	missense	Exon 6 of 6	ENSP00000274382.4	Q8N485
	LIX1	ENST00000942939.1		c.595G>A	p.Ala199Thr	missense	Exon 6 of 6	ENSP00000612998.1
	LIX1-AS1	ENST00000504578.2	TSL:5	n.130+5774C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461858 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.029	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-3.7	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.41		Loss of helix (P = 0.0237)
MVP		0.64
MPC		0.76
ClinPred		0.98	D
GERP RS		6.0
Varity_R		0.68
gMVP		0.49
Mutation Taster		=10/90	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2112743524; hg19: chr5-96430682;