3-169851743-T-G

Variant names:

• chr3-169851743-T-G
• rs1159257303
• NM_024727.4:c.1035A>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_024727.4(LRRC31):​c.1035A>C​(p.Leu345Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: LRRC31 NM_024727.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.435
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.843

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.1035A>C	p.Leu345Phe	missense	Exon 7 of 9	NP_079003.2	Q6UY01-1
	LRRC31	NM_001277128.2		c.867A>C	p.Leu289Phe	missense	Exon 6 of 8	NP_001264057.1	Q6UY01-2
	LRRC31	NM_001277127.2		c.1035A>C	p.Leu345Phe	missense	Exon 7 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.1035A>C	p.Leu345Phe	missense	Exon 7 of 9	ENSP00000325978.5	Q6UY01-1
	LRRC31	ENST00000523069.1	TSL:1	c.1035A>C	p.Leu345Phe	missense	Exon 7 of 9	ENSP00000429145.1	Q6UY01-4
	LRRC31	ENST00000945890.1		c.1011A>C	p.Leu337Phe	missense	Exon 7 of 9	ENSP00000615949.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000801 AC: 2 AN: 249562 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461864 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111992

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152204 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74368

African (AFR) AF: 0.00 AC: 0 AN: 41450

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

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	0.24
BayesDel_addAF	Uncertain	0.087	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.071	T
Eigen	Benign	-0.048
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.90	D
M_CAP	Uncertain	0.096	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		0.43
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.55
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.72		Gain of glycosylation at S346 (P = 0.0575)
MVP		0.80
MPC		0.24
ClinPred		0.97	D
GERP RS		-1.3
Varity_R		0.21
gMVP		0.53
Mutation Taster		=81/19	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

dbSNP: rs1159257303; hg19: chr3-169569531;