10-132337566-A-G

Variant names:

• chr10-132337566-A-G
• rs1369095756
• NM_030626.3:c.212A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030626.3(LRRC27):​c.212A>G​(p.Gln71Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 18/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: LRRC27 NM_030626.3 missense, splice_region
• Scores: Splicing: ADA: 0.06462
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.15
• Publications: 0 publications found

Genes affected

LRRC27 (HGNC:29346): (leucine rich repeat containing 27)

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=0.2737671).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030626.3. 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
	LRRC27	NM_030626.3	MANE Select	c.212A>G	p.Gln71Arg	missense splice_region	Exon 3 of 11	NP_085129.1	Q9C0I9-1
	LRRC27	NM_001143757.2		c.212A>G	p.Gln71Arg	missense splice_region	Exon 3 of 11	NP_001137229.1	Q9C0I9-1
	LRRC27	NM_001143758.2		c.212A>G	p.Gln71Arg	missense splice_region	Exon 3 of 8	NP_001137230.1	Q9C0I9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC27	ENST00000368614.8	TSL:1 MANE Select	c.212A>G	p.Gln71Arg	missense splice_region	Exon 3 of 11	ENSP00000357603.3	Q9C0I9-1
	LRRC27	ENST00000368613.8	TSL:1	c.212A>G	p.Gln71Arg	missense splice_region	Exon 3 of 11	ENSP00000357602.4	Q9C0I9-1
	LRRC27	ENST00000625755.2	TSL:1	c.212A>G	p.Gln71Arg	missense splice_region	Exon 3 of 8	ENSP00000486582.1	Q9C0I9-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 33

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

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152224 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74374

African (AFR) AF: 0.00 AC: 0 AN: 41446

American (AMR) AF: 0.00 AC: 0 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

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	0.29
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.047	T
Eigen	Benign	0.058
Eigen_PC	Benign	0.089
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.97	L
PhyloP100		3.1
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.10
Sift	Benign	0.073	T
Sift4G	Uncertain	0.043	D
Polyphen		0.99	D
Vest4		0.38
MutPred		0.39		Gain of catalytic residue at Q71 (P = 0.0254)
MVP		0.32
MPC		0.37
ClinPred		0.85	D
GERP RS		4.7
Varity_R		0.16
gMVP		0.27
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.065
dbscSNV1_RF	Benign	0.38
SpliceAI score (max)		0.040		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: rs1369095756; hg19: chr10-134151070;