3-169851639-C-G

Position:

• chr3-169851639-C-G

Variant summary

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

The NM_024727.4(LRRC31):​c.1139G>C​(p.Ser380Thr) 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. 16/21 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: LRRC31 NM_024727.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0570

Genes affected

LRRC31 (HGNC:26261): (leucine rich repeat containing 31)

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=0.08103588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC31	NM_024727.4	c.1139G>C	p.Ser380Thr	missense_variant	7/9	ENST00000316428.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC31	ENST00000316428.10	c.1139G>C	p.Ser380Thr	missense_variant	7/9	1	NM_024727.4	P1
LRRC31	ENST00000523069.1	c.1139G>C	p.Ser380Thr	missense_variant	7/9	1
LRRC31	ENST00000264676.9	c.971G>C	p.Ser324Thr	missense_variant	6/8	2

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 14, 2023

The c.1139G>C (p.S380T) alteration is located in exon 8 (coding exon 7) of the LRRC31 gene. This alteration results from a G to C substitution at nucleotide position 1139, causing the serine (S) at amino acid position 380 to be replaced by a threonine (T). 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	0.074
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	1.2
DANN	Benign	0.69
DEOGEN2	Benign	0.0042	T;.;.
Eigen	Benign	-0.90
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.048	N
LIST_S2	Benign	0.33	T;T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.081	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.40	N;.;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.87	N;N;N
REVEL	Benign	0.067
Sift	Benign	0.51	T;T;T
Sift4G	Benign	0.40	T;T;T
Polyphen		0.0040	B;B;.
Vest4		0.14
MutPred		0.36		Loss of glycosylation at S380 (P = 0.1166);.;Loss of glycosylation at S380 (P = 0.1166);
MVP		0.38
MPC		0.028
ClinPred		0.081	T
GERP RS		0.65
Varity_R		0.079
gMVP		0.16

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: chr3-169569427;