chr6-143857380-C-T

Variant names:

• chr6-143857380-C-T
• rs1226129332
• NM_032860.5:c.475C>T

Variant summary

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

The NM_032860.5(LTV1):​c.475C>T​(p.Leu159Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LTV1 NM_032860.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.52

Genes affected

LTV1 (HGNC:21173): (LTV1 ribosome biogenesis factor) Predicted to be involved in ribosomal small subunit biogenesis and ribosomal small subunit export from nucleus. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000280148 (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 rank	MANE	Protein	UniProt
LTV1	NM_032860.5	c.475C>T	p.Leu159Phe	missense_variant	Exon 5 of 11	ENST00000367576.6	NP_116249.2
LTV1	NM_001329953.2	c.-202C>T		5_prime_UTR_variant	Exon 5 of 11		NP_001316882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTV1	ENST00000367576.6	c.475C>T	p.Leu159Phe	missense_variant	Exon 5 of 11	1	NM_032860.5	ENSP00000356548.5
ENSG00000280148	ENST00000454207.2	n.-54C>T		non_coding_transcript_exon_variant	Exon 1 of 10	2		ENSP00000400756.2
ENSG00000280148	ENST00000454207.2	n.-54C>T		5_prime_UTR_variant	Exon 1 of 10	2		ENSP00000400756.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461796 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727200

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000986 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 13, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.475C>T (p.L159F) alteration is located in exon 5 (coding exon 5) of the LTV1 gene. This alteration results from a C to T substitution at nucleotide position 475, causing the leucine (L) at amino acid position 159 to be replaced by a phenylalanine (F). 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	0.63
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.22	T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.77
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Uncertain	-0.050	T
MutationAssessor	Pathogenic	3.0	M
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.63
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.56
MVP		0.82
MPC		0.58
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.80
gMVP		0.19

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: rs1226129332; hg19: chr6-144178517;