chr15-70832939-G-C

Position:

• chr15-70832939-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018357.4(LARP6):​c.589C>G​(p.Leu197Val) 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. 13/21 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)
• Consequence: LARP6 NM_018357.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.79

Genes affected

LARP6 (HGNC:24012): (La ribonucleoprotein 6, translational regulator) Enables RNA binding activity and myosin binding activity. Involved in positive regulation of collagen biosynthetic process; positive regulation of mRNA binding activity; and positive regulation of translation. Located in nucleus. Part of polysome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15205812).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LARP6	NM_018357.4	c.589C>G	p.Leu197Val	missense_variant	3/3	ENST00000299213.10
LARP6	NM_001286679.2	c.37C>G	p.Leu13Val	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LARP6	ENST00000299213.10	c.589C>G	p.Leu197Val	missense_variant	3/3	1	NM_018357.4	P1
LARP6	ENST00000559316.2	c.37C>G	p.Leu13Val	missense_variant	3/3	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000476 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2021

The c.589C>G (p.L197V) alteration is located in exon 3 (coding exon 3) of the LARP6 gene. This alteration results from a C to G substitution at nucleotide position 589, causing the leucine (L) at amino acid position 197 to be replaced by a valine (V). 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	0.081
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T;T
Eigen	Benign	-0.041
Eigen_PC	Benign	-0.10
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;.
MutationTaster	Benign	0.65	N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.66	N;.
REVEL	Benign	0.099
Sift	Benign	0.10	T;.
Sift4G	Benign	0.096	T;.
Polyphen		0.98	D;.
Vest4		0.096
MutPred		0.44		Gain of sheet (P = 0.0149);.;
MVP		0.30
MPC		0.48
ClinPred		0.25	T
GERP RS		2.3
Varity_R		0.049
gMVP		0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs2032082136; hg19: chr15-71125278;