6-143857802-A-G

Variant names:

• chr6-143857802-A-G
• rs774113447
• NM_032860.5:c.590A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032860.5(LTV1):​c.590A>G​(p.Lys197Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K197T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LTV1 NM_032860.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.836
• Publications: 0 publications found

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]

LTV1 Gene-Disease associations (from GenCC):

• inflammatory poikiloderma with hair abnormalities and acral keratoses

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ENSG00000280148 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054341137).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032860.5. 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
	LTV1	NM_032860.5	MANE Select	c.590A>G	p.Lys197Arg	missense	Exon 6 of 11	NP_116249.2
	LTV1	NM_001329953.2		c.53A>G	p.Lys18Arg	missense	Exon 6 of 11	NP_001316882.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LTV1	ENST00000367576.6	TSL:1 MANE Select	c.590A>G	p.Lys197Arg	missense	Exon 6 of 11	ENSP00000356548.5	Q96GA3
	ENSG00000280148	ENST00000454207.2	TSL:2	n.62A>G		non_coding_transcript_exon	Exon 2 of 10	ENSP00000400756.2	A0A075B6Q4
	LTV1	ENST00000970779.1		c.647A>G	p.Lys216Arg	missense	Exon 6 of 11	ENSP00000640838.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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	Benign	0.077
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	12
DANN	Benign	0.92
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.84
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.014
Sift	Benign	0.45	T
Sift4G	Benign	0.48	T
Polyphen		0.0040	B
Vest4		0.077
MutPred		0.33		Loss of ubiquitination at K197 (P = 0.0022)
MVP		0.43
MPC		0.13
ClinPred		0.018	T
GERP RS		1.1
Varity_R		0.016
gMVP		0.031
Mutation Taster		=96/4	polymorphism

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: rs774113447; hg19: chr6-144178939;