3-169856387-C-G

Position:

• chr3-169856387-C-G

Variant summary

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

The NM_024727.4(LRRC31):​c.772G>C​(p.Val258Leu) 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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: LRRC31 NM_024727.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.76

Genes affected

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

LRRC31 (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=0.40238836).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC31	NM_024727.4	c.772G>C	p.Val258Leu	missense_variant	5/9	ENST00000316428.10	NP_079003.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC31	ENST00000316428.10	c.772G>C	p.Val258Leu	missense_variant	5/9	1	NM_024727.4	ENSP00000325978.5
LRRC31	ENST00000523069.1	c.772G>C	p.Val258Leu	missense_variant	5/9	1		ENSP00000429145.1
LRRC31	ENST00000264676.9	c.604G>C	p.Val202Leu	missense_variant	4/8	2		ENSP00000264676.5
LRRC31	ENST00000397805.2	n.839G>C		non_coding_transcript_exon_variant	5/7	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

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

Oct 21, 2024

The c.772G>C (p.V258L) alteration is located in exon 6 (coding exon 5) of the LRRC31 gene. This alteration results from a G to C substitution at nucleotide position 772, causing the valine (V) at amino acid position 258 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	0.23
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.0089	T;.;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.74	T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.40	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;.;M
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.25	T;T;T
Sift4G	Benign	0.30	T;T;T
Polyphen		0.87	P;P;.
Vest4		0.26
MutPred		0.45		Loss of helix (P = 0.0376);.;Loss of helix (P = 0.0376);
MVP		0.44
MPC		0.095
ClinPred		0.28	T
GERP RS		0.74
Varity_R		0.10
gMVP		0.22

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: chr3-169574175;