12-50453622-G-T

Position:

• chr12-50453622-G-T

Variant summary

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

The NM_052879.5(LARP4):​c.967G>T​(p.Val323Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: LARP4 NM_052879.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.14

Genes affected

LARP4 (HGNC:24320): (La ribonucleoprotein 4) Enables mRNA 3'-UTR binding activity and poly(A) binding activity. Involved in cytoskeleton organization; positive regulation of translation; and regulation of cell morphogenesis. Located in cytosol. Colocalizes with cytoplasmic stress granule; cytosolic small ribosomal subunit; and polysome. [provided by Alliance of Genome Resources, Apr 2022]

LARP4 (HGNC:):

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=0.22633967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LARP4	NM_052879.5	c.967G>T	p.Val323Leu	missense_variant	9/16	ENST00000398473.7	NP_443111.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LARP4	ENST00000398473.7	c.967G>T	p.Val323Leu	missense_variant	9/16	1	NM_052879.5	ENSP00000381490.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

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

Oct 29, 2021

The c.967G>T (p.V323L) alteration is located in exon 9 (coding exon 9) of the LARP4 gene. This alteration results from a G to T substitution at nucleotide position 967, causing the valine (V) at amino acid position 323 to be replaced by a leucine (L). 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	0.17
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.040	.;.;T;.;.;.;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.079
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.83	T;T;T;T;T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.23	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;L;L;.;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N;.
REVEL	Benign	0.13
Sift	Benign	0.11	T;T;T;T;T;T;.
Sift4G	Benign	0.13	T;T;T;T;T;T;T
Polyphen		0.052, 0.026, 0.019	.;B;B;.;B;.;.
Vest4		0.68
MutPred		0.26		Gain of catalytic residue at P324 (P = 5e-04);.;Gain of catalytic residue at P324 (P = 5e-04);Gain of catalytic residue at P324 (P = 5e-04);.;.;.;
MVP		0.65
MPC		0.27
ClinPred		0.84	D
GERP RS		3.0
Varity_R		0.14
gMVP		0.85

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-50847405;