3-169856387-C-G

Variant names:

• chr3-169856387-C-G
• NM_024727.4:c.772G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40238836).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024727.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC31	NM_024727.4	MANE Select	c.772G>C	p.Val258Leu	missense	Exon 5 of 9	NP_079003.2	Q6UY01-1
	LRRC31	NM_001277128.2		c.604G>C	p.Val202Leu	missense	Exon 4 of 8	NP_001264057.1	Q6UY01-2
	LRRC31	NM_001277127.2		c.772G>C	p.Val258Leu	missense	Exon 5 of 9	NP_001264056.1	Q6UY01-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC31	ENST00000316428.10	TSL:1 MANE Select	c.772G>C	p.Val258Leu	missense	Exon 5 of 9	ENSP00000325978.5	Q6UY01-1
	LRRC31	ENST00000523069.1	TSL:1	c.772G>C	p.Val258Leu	missense	Exon 5 of 9	ENSP00000429145.1	Q6UY01-4
	LRRC31	ENST00000945890.1		c.748G>C	p.Val250Leu	missense	Exon 5 of 9	ENSP00000615949.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M
PhyloP100		1.8
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.14
Sift	Benign	0.25	T
Sift4G	Benign	0.30	T
Polyphen		0.87	P
Vest4		0.26
MutPred		0.45		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
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr3-169574175;