4-128077918-A-T

Variant names:

• chr4-128077918-A-T
• NM_018078.4:c.173A>T

Variant summary

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

The NM_018078.4(LARP1B):​c.173A>T​(p.Asn58Ile) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LARP1B NM_018078.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04

Genes affected

LARP1B (HGNC:24704): (La ribonucleoprotein 1B) This gene encodes a protein containing domains found in the La related protein of Drosophila melanogaster. La motif-containing proteins are thought to be RNA-binding proteins, where the La motif and adjacent amino acids fold into an RNA recognition motif. The La motif is also found in proteins unrelated to the La protein. Alternative splicing has been observed at this locus and multiple variants, encoding distinct isoforms, are described. Additional splice variation has been identified but the full-length nature of these transcripts has not been determined. [provided by RefSeq, Jun 2013]

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=0.15396783).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LARP1B	NM_018078.4	c.173A>T	p.Asn58Ile	missense_variant	Exon 4 of 20	ENST00000326639.11	NP_060548.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LARP1B	ENST00000326639.11	c.173A>T	p.Asn58Ile	missense_variant	Exon 4 of 20	5	NM_018078.4	ENSP00000321997.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 18, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.173A>T (p.N58I) alteration is located in exon 4 (coding exon 2) of the LARP1B gene. This alteration results from a A to T substitution at nucleotide position 173, causing the asparagine (N) at amino acid position 58 to be replaced by an isoleucine (I). 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	0.095
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.044	T;.;.;.;T;.;.;.
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.77	T;T;T;T;T;T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.15	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.;.;M;.;.;.;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.4	N;N;N;N;N;.;.;.
REVEL	Benign	0.075
Sift	Benign	0.039	D;D;D;D;D;.;.;.
Sift4G	Benign	0.15	T;T;T;T;T;.;.;.
Polyphen		0.96	D;.;.;P;P;.;.;.
Vest4		0.41
MutPred		0.26		Gain of glycosylation at S60 (P = 0.0068);Gain of glycosylation at S60 (P = 0.0068);Gain of glycosylation at S60 (P = 0.0068);Gain of glycosylation at S60 (P = 0.0068);Gain of glycosylation at S60 (P = 0.0068);.;.;.;
MVP		0.44
MPC		0.25
ClinPred		0.51	D
GERP RS		2.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr4-128999073;