10-132348079-G-C

Variant names:

• chr10-132348079-G-C
• rs147220999
• NM_030626.3:c.649G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030626.3(LRRC27):​c.649G>C​(p.Ala217Pro) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A217T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: LRRC27 NM_030626.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 1 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061939716).

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.649G>C	p.Ala217Pro	missense	Exon 6 of 11	NP_085129.1	Q9C0I9-1
	LRRC27	NM_001143757.2		c.649G>C	p.Ala217Pro	missense	Exon 6 of 11	NP_001137229.1	Q9C0I9-1
	LRRC27	NM_001143758.2		c.649G>C	p.Ala217Pro	missense	Exon 6 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.649G>C	p.Ala217Pro	missense	Exon 6 of 11	ENSP00000357603.3	Q9C0I9-1
	LRRC27	ENST00000368613.8	TSL:1	c.649G>C	p.Ala217Pro	missense	Exon 6 of 11	ENSP00000357602.4	Q9C0I9-1
	LRRC27	ENST00000625755.2	TSL:1	c.649G>C	p.Ala217Pro	missense	Exon 6 of 8	ENSP00000486582.1	Q9C0I9-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.089
DANN	Benign	0.97
DEOGEN2	Benign	0.028	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0081	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-1.3
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.015
Sift	Benign	0.17	T
Sift4G	Benign	0.26	T
Polyphen		0.062	B
Vest4		0.060
MutPred		0.32		Loss of loop (P = 0.1242)
MVP		0.15
MPC		0.43
ClinPred		0.15	T
GERP RS		-5.2
Varity_R		0.052
gMVP		0.36
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs147220999; hg19: chr10-134161583;