6-143857832-C-A

Variant names:

• chr6-143857832-C-A
• rs1777103438
• NM_032860.5:c.620C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032860.5(LTV1):​c.620C>A​(p.Ala207Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. 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: 3.05

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.064882755).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LTV1	NM_032860.5	c.620C>A	p.Ala207Glu	missense_variant	Exon 6 of 11	ENST00000367576.6	NP_116249.2
LTV1	NM_001329953.2	c.83C>A	p.Ala28Glu	missense_variant	Exon 6 of 11		NP_001316882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LTV1	ENST00000367576.6	c.620C>A	p.Ala207Glu	missense_variant	Exon 6 of 11	1	NM_032860.5	ENSP00000356548.5
ENSG00000280148	ENST00000454207.2	n.92C>A		non_coding_transcript_exon_variant	Exon 2 of 10	2		ENSP00000400756.2
ENSG00000270890	ENST00000604280.1	n.*230G>T		downstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461778 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727206

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

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 15, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.620C>A (p.A207E) alteration is located in exon 6 (coding exon 6) of the LTV1 gene. This alteration results from a C to A substitution at nucleotide position 620, causing the alanine (A) at amino acid position 207 to be replaced by a glutamic acid (E). 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	Benign	0.087
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.5
DANN	Benign	0.25
DEOGEN2	Benign	0.0028	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.93
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.065	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.83	N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.067
MutPred		0.63		Gain of solvent accessibility (P = 0.0246);
MVP		0.16
MPC		0.13
ClinPred		0.029	T
GERP RS		2.8
Varity_R		0.027
gMVP		0.067

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: rs1777103438; hg19: chr6-144178969; COSMIC: COSV62536518; COSMIC: COSV62536518;