chr15-70854064-G-A

Position:

• chr15-70854064-G-A

Variant summary

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

The NM_018357.4(LARP6):​c.25C>T​(p.Arg9Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000812 in 1,231,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: LARP6 NM_018357.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.900

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]

LRRC49 (HGNC:25965): (leucine rich repeat containing 49) Predicted to be involved in outer dynein arm assembly. Predicted to be located in microtubule. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

LRRC49 (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=0.055426657).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARP6	NM_018357.4	c.25C>T	p.Arg9Trp	missense_variant	1/3	ENST00000299213.10	NP_060827.2
LARP6	NM_197958.3	c.25C>T	p.Arg9Trp	missense_variant	1/2		NP_932062.1
LRRC49	NM_001284357.2	c.-299+595G>A		intron_variant			NP_001271286.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LARP6	ENST00000299213.10	c.25C>T	p.Arg9Trp	missense_variant	1/3	1	NM_018357.4	ENSP00000299213.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 8.12e-7 AC: 1 AN: 1231294 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 603350

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000466

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Sep 01, 2024

The c.25C>T (p.R9W) alteration is located in exon 1 (coding exon 1) of the LARP6 gene. This alteration results from a C to T substitution at nucleotide position 25, causing the arginine (R) at amino acid position 9 to be replaced by a tryptophan (W). 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	0.14
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.69	T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.055	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.26	N;N
REVEL	Benign	0.057
Sift	Uncertain	0.023	D;D
Sift4G	Benign	0.081	T;T
Polyphen		0.0	B;.
Vest4		0.080
MutPred		0.30		Gain of catalytic residue at P12 (P = 0.0203);Gain of catalytic residue at P12 (P = 0.0203);
MVP		0.11
MPC		0.57
ClinPred		0.056	T
GERP RS		-3.0
Varity_R		0.14
gMVP		0.23

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: rs1173032281; hg19: chr15-71146403;