15-42547328-T-A

Variant names:

• chr15-42547328-T-A
• NM_153260.3:c.425A>T

Variant summary

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

The NM_153260.3(LRRC57):​c.425A>T​(p.Gln142Leu) 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. 14/21 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: LRRC57 NM_153260.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.18

Genes affected

LRRC57 (HGNC:26719): (leucine rich repeat containing 57) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000285942 (HGNC:):

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=0.28753477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC57	NM_153260.3	c.425A>T	p.Gln142Leu	missense_variant	Exon 4 of 6	ENST00000397130.8	NP_694992.2
LRRC57	XM_047432335.1	c.425A>T	p.Gln142Leu	missense_variant	Exon 4 of 6		XP_047288291.1
LRRC57	XM_011521423.4	c.425A>T	p.Gln142Leu	missense_variant	Exon 4 of 6		XP_011519725.1
LRRC57	XM_011521424.4	c.425A>T	p.Gln142Leu	missense_variant	Exon 4 of 6		XP_011519726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC57	ENST00000397130.8	c.425A>T	p.Gln142Leu	missense_variant	Exon 4 of 6	1	NM_153260.3	ENSP00000380319.3
ENSG00000285942	ENST00000650210.1	n.425A>T		non_coding_transcript_exon_variant	Exon 4 of 9			ENSP00000497618.1

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 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.425A>T (p.Q142L) alteration is located in exon 4 (coding exon 3) of the LRRC57 gene. This alteration results from a A to T substitution at nucleotide position 425, causing the glutamine (Q) at amino acid position 142 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	0.14
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;T;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.033
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.91	.;.;D;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.72	N;N;N;.
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.3	D;D;D;D
REVEL	Benign	0.11
Sift	Benign	0.10	T;T;T;T
Sift4G	Benign	0.20	T;T;T;.
Polyphen		0.023	B;B;B;.
Vest4		0.58
MutPred		0.41		Loss of disorder (P = 0.0377);Loss of disorder (P = 0.0377);Loss of disorder (P = 0.0377);Loss of disorder (P = 0.0377);
MVP		0.77
MPC		0.32
ClinPred		0.56	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr15-42839526;