chr10-132348154-G-C

Position:

• chr10-132348154-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000368614.8(LRRC27):​c.724G>C​(p.Glu242Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRRC27 ENST00000368614.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11014539).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC27	NM_030626.3	c.724G>C	p.Glu242Gln	missense_variant	6/11	ENST00000368614.8	NP_085129.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LRRC27	ENST00000368614.8	c.724G>C	p.Glu242Gln	missense_variant	6/11	1	NM_030626.3	ENSP00000357603	P2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 21, 2023

The c.724G>C (p.E242Q) alteration is located in exon 6 (coding exon 5) of the LRRC27 gene. This alteration results from a G to C substitution at nucleotide position 724, causing the glutamic acid (E) at amino acid position 242 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;.;T;T;.
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.82	T;T;.;T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.11	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L;L;L;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N;.;N;N;N
REVEL	Benign	0.073
Sift	Benign	0.031	D;.;D;D;D
Sift4G	Benign	0.10	T;T;T;T;T
Polyphen		0.76	P;P;P;P;P
Vest4		0.21
MutPred		0.20		Gain of methylation at K237 (P = 0.1648);Gain of methylation at K237 (P = 0.1648);Gain of methylation at K237 (P = 0.1648);Gain of methylation at K237 (P = 0.1648);.;
MVP		0.24
MPC		0.079
ClinPred		0.40	T
GERP RS		3.0
Varity_R		0.14
gMVP		0.28

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-134161658;