rs769558664

Variant names:

• chr5-97124624-C-A
• rs769558664
• NM_153234.5:c.88G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-97124624-C-A
• chr5-97124624-C-T

Variant summary

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

The NM_153234.5(LIX1):​c.88G>T​(p.Val30Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,688 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V30I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LIX1 NM_153234.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.77
• 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 2 ACMG points.

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

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.88G>T	p.Val30Phe	missense	Exon 2 of 6	NP_694966.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIX1	ENST00000274382.9	TSL:1 MANE Select	c.88G>T	p.Val30Phe	missense	Exon 2 of 6	ENSP00000274382.4	Q8N485
	LIX1	ENST00000942939.1		c.88G>T	p.Val30Phe	missense	Exon 2 of 6	ENSP00000612998.1
	LIX1	ENST00000512378.1	TSL:5	c.16G>T	p.Val6Phe	missense	Exon 3 of 4	ENSP00000427469.1	D6RID5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455688 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 723934

African (AFR) AF: 0.0000301 AC: 1 AN: 33230

American (AMR) AF: 0.00 AC: 0 AN: 43954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25966

East Asian (EAS) AF: 0.00 AC: 0 AN: 39508

South Asian (SAS) AF: 0.00 AC: 0 AN: 85122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108802

Other (OTH) AF: 0.00 AC: 0 AN: 60132

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		6.8
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.37		Gain of helix (P = 0.0854)
MVP		0.59
MPC		0.91
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.79
gMVP		0.82
Mutation Taster		=6/94	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs769558664; hg19: chr5-96460328;