Genetic Variant LRRC57:p.Ser91Asn (chr15-42547481-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153260.3(LRRC57):c.272G>A(p.Ser91Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

LRRC57
NM_153260.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.79

Variant links:

Genes affected

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

LRRC57 links:

ENSG00000285942 (HGNC:):

ENSG00000285942 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.16326463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC57	NM_153260.3 link	c.272G>A	p.Ser91Asn	missense_variant	Exon 4 of 6	ENST00000397130.8	NP_694992.2	Q8N9N7A0A024R9M3
LRRC57	XM_047432335.1 link	c.272G>A	p.Ser91Asn	missense_variant	Exon 4 of 6		XP_047288291.1
LRRC57	XM_011521423.4 link	c.272G>A	p.Ser91Asn	missense_variant	Exon 4 of 6		XP_011519725.1
LRRC57	XM_011521424.4 link	c.272G>A	p.Ser91Asn	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 link	c.272G>A	p.Ser91Asn	missense_variant	Exon 4 of 6	1	NM_153260.3	ENSP00000380319.3		Q8N9N7
ENSG00000285942	ENST00000650210.1 link	n.272G>A		non_coding_transcript_exon_variant	Exon 4 of 9			ENSP00000497618.1		A0A3B3ISV5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000801

AC:

AN:

249782

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135114

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461624

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.272G>A (p.S91N) alteration is located in exon 4 (coding exon 3) of the LRRC57 gene. This alteration results from a G to A substitution at nucleotide position 272, causing the serine (S) at amino acid position 91 to be replaced by an asparagine (N). 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

0.13

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.015

T;T;T;.

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.82

.;.;T;D

M_CAP

Benign

0.0057

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

N;N;N;.

PrimateAI

Uncertain

0.53

PROVEAN

Benign

1.2

N;N;N;N

REVEL

Benign

0.044

Sift

Benign

0.56

T;T;T;T

Sift4G

Benign

0.51

T;T;T;.

Polyphen

0.017

B;B;B;.

Vest4

0.41

MutPred

0.35

Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);

MVP

0.61

MPC

0.31

ClinPred

0.16

GERP RS

3.3

Varity_R

0.046

gMVP

0.25

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over