chr15-70832671-A-G

Position:

• chr15-70832671-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_018357.4(LARP6):​c.857T>C​(p.Met286Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 8.80

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36040515).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LARP6	NM_018357.4	c.857T>C	p.Met286Thr	missense_variant	3/3	ENST00000299213.10
LARP6	NM_001286679.2	c.305T>C	p.Met102Thr	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LARP6	ENST00000299213.10	c.857T>C	p.Met286Thr	missense_variant	3/3	1	NM_018357.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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 29, 2023

The c.857T>C (p.M286T) alteration is located in exon 3 (coding exon 3) of the LARP6 gene. This alteration results from a T to C substitution at nucleotide position 857, causing the methionine (M) at amino acid position 286 to be replaced by a threonine (T). 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	Uncertain	0.41
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.98	D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.21
Sift	Uncertain	0.012	D
Sift4G	Uncertain	0.047	D
Polyphen		0.26	B
Vest4		0.59
MutPred		0.44		Gain of sheet (P = 0.0101);
MVP		0.12
MPC		0.82
ClinPred		0.89	D
GERP RS		5.0
Varity_R		0.34
gMVP		0.60

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: rs2032072401; hg19: chr15-71125010;