chr3-169848231-A-C

Variant names:

• chr3-169848231-A-C
• NM_024727.4:c.1216T>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024727.4(LRRC31):​c.1216T>G​(p.Cys406Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 6.22
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.825

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.1216T>G	p.Cys406Gly	missense	Exon 8 of 9	NP_079003.2	Q6UY01-1
	LRRC31	NM_001277128.2		c.1048T>G	p.Cys350Gly	missense	Exon 7 of 8	NP_001264057.1	Q6UY01-2
	LRRC31	NM_001277127.2		c.1216T>G	p.Cys406Gly	missense	Exon 8 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.1216T>G	p.Cys406Gly	missense	Exon 8 of 9	ENSP00000325978.5	Q6UY01-1
	LRRC31	ENST00000523069.1	TSL:1	c.1216T>G	p.Cys406Gly	missense	Exon 8 of 9	ENSP00000429145.1	Q6UY01-4
	LRRC31	ENST00000945890.1		c.1192T>G	p.Cys398Gly	missense	Exon 8 of 9	ENSP00000615949.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.16
BayesDel_addAF	Uncertain	0.046	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.054	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.37
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		6.2
PrimateAI	Benign	0.45	T
PROVEAN	Pathogenic	-5.5	D
REVEL	Benign	0.28
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.012	D
Polyphen		0.99	D
Vest4		0.70
MutPred		0.70		Loss of methylation at K405 (P = 0.0192)
MVP		0.69
MPC		0.23
ClinPred		0.98	D
GERP RS		4.6
Varity_R		0.69
gMVP		0.82
Mutation Taster		=73/27	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: chr3-169566019;