10-132333684-G-C

Position:

• chr10-132333684-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_030626.3(LRRC27):​c.160G>C​(p.Glu54Gln) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRRC27 NM_030626.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.168

Genes affected

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

LRRC27 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.022380978).
• BP6: Variant 10-132333684-G-C is Benign according to our data. Variant chr10-132333684-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2239007.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC27	NM_030626.3	c.160G>C	p.Glu54Gln	missense_variant	2/11	ENST00000368614.8	NP_085129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC27	ENST00000368614.8	c.160G>C	p.Glu54Gln	missense_variant	2/11	1	NM_030626.3	ENSP00000357603.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.4
DANN	Benign	0.64
DEOGEN2	Benign	0.013	.;.;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.54	T;T;.;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.022	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.4	N;N;N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.72	N;.;N;N
REVEL	Benign	0.020
Sift	Benign	1.0	T;.;T;T
Sift4G	Benign	1.0	T;T;T;T
Polyphen		0.017	B;B;B;B
Vest4		0.075
MutPred		0.30		Loss of phosphorylation at S53 (P = 0.1136);Loss of phosphorylation at S53 (P = 0.1136);Loss of phosphorylation at S53 (P = 0.1136);Loss of phosphorylation at S53 (P = 0.1136);
MVP		0.048
MPC		0.061
ClinPred		0.022	T
GERP RS		-0.13
Varity_R		0.054
gMVP		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-134147188;