15-42548121-T-C

Variant names:

• chr15-42548121-T-C
• NM_153260.3:c.208A>G

Variant summary

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

The NM_153260.3(LRRC57):​c.208A>G​(p.Asn70Asp) 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: 32)
• Consequence: LRRC57 NM_153260.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.87

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=0.29146358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC57	NM_153260.3	c.208A>G	p.Asn70Asp	missense_variant	Exon 3 of 6	ENST00000397130.8	NP_694992.2
LRRC57	XM_047432335.1	c.208A>G	p.Asn70Asp	missense_variant	Exon 3 of 6		XP_047288291.1
LRRC57	XM_011521423.4	c.208A>G	p.Asn70Asp	missense_variant	Exon 3 of 6		XP_011519725.1
LRRC57	XM_011521424.4	c.208A>G	p.Asn70Asp	missense_variant	Exon 3 of 6		XP_011519726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC57	ENST00000397130.8	c.208A>G	p.Asn70Asp	missense_variant	Exon 3 of 6	1	NM_153260.3	ENSP00000380319.3
ENSG00000285942	ENST00000650210.1	n.208A>G		non_coding_transcript_exon_variant	Exon 3 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

Jun 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.208A>G (p.N70D) alteration is located in exon 3 (coding exon 2) of the LRRC57 gene. This alteration results from a A to G substitution at nucleotide position 208, causing the asparagine (N) at amino acid position 70 to be replaced by an aspartic acid (D). 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	0.21
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.047	T;T;T;.
Eigen	Benign	-0.016
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.92	.;.;D;D
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.29	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N;N;.
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.084
Sift	Benign	0.12	T;T;T;T
Sift4G	Benign	0.43	T;T;T;.
Polyphen		0.21	B;B;B;.
Vest4		0.71
MutPred		0.38		Gain of ubiquitination at K65 (P = 0.0389);Gain of ubiquitination at K65 (P = 0.0389);Gain of ubiquitination at K65 (P = 0.0389);Gain of ubiquitination at K65 (P = 0.0389);
MVP		0.72
MPC		0.80
ClinPred		0.95	D
GERP RS		5.2
Varity_R		0.29
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-42840319;