10-132348079-G-T

Variant names:

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

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>T​(p.Ala217Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,806 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• 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=0.04351428).

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>T	p.Ala217Ser	missense	Exon 6 of 11	NP_085129.1	Q9C0I9-1
	LRRC27	NM_001143757.2		c.649G>T	p.Ala217Ser	missense	Exon 6 of 11	NP_001137229.1	Q9C0I9-1
	LRRC27	NM_001143758.2		c.649G>T	p.Ala217Ser	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>T	p.Ala217Ser	missense	Exon 6 of 11	ENSP00000357603.3	Q9C0I9-1
	LRRC27	ENST00000368613.8	TSL:1	c.649G>T	p.Ala217Ser	missense	Exon 6 of 11	ENSP00000357602.4	Q9C0I9-1
	LRRC27	ENST00000625755.2	TSL:1	c.649G>T	p.Ala217Ser	missense	Exon 6 of 8	ENSP00000486582.1	Q9C0I9-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251400 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461806 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727202

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

American (AMR) AF: 0.00 AC: 0 AN: 44722

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53358

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112010

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.0060
DANN	Benign	0.48
DEOGEN2	Benign	0.0093	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0012	N
LIST_S2	Benign	0.64	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.13	N
PhyloP100		-1.3
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.46	N
REVEL	Benign	0.0070
Sift	Benign	0.63	T
Sift4G	Benign	0.59	T
Polyphen		0.10	B
Vest4		0.029
MutPred		0.23		Gain of phosphorylation at A217 (P = 0.0399)
MVP		0.13
MPC		0.36
ClinPred		0.018	T
GERP RS		-5.2
Varity_R		0.037
gMVP		0.28
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;