11-61509077-G-C

Variant names:

• chr11-61509077-G-C
• NM_001145077.2:c.79G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001145077.2(LRRC10B):​c.79G>C​(p.Glu27Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000735 in 1,359,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: LRRC10B NM_001145077.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.26

Genes affected

LRRC10B (HGNC:37215): (leucine rich repeat containing 10B)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30894956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC10B	NM_001145077.2	c.79G>C	p.Glu27Gln	missense_variant	Exon 1 of 1	ENST00000378075.4	NP_001138549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC10B	ENST00000378075.4	c.79G>C	p.Glu27Gln	missense_variant	Exon 1 of 1	6	NM_001145077.2	ENSP00000367315.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.35e-7 AC: 1 AN: 1359726 Hom.: 0 Cov.: 33 AF XY: 0.00000149 AC XY: 1 AN XY: 670666

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.34e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 24, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.79G>C (p.E27Q) alteration is located in exon 1 (coding exon 1) of the LRRC10B gene. This alteration results from a G to C substitution at nucleotide position 79, causing the glutamic acid (E) at amino acid position 27 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	Uncertain	0.50
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.13
Sift	Benign	0.10	T
Sift4G	Uncertain	0.048	D
Polyphen		0.97	D
Vest4		0.18
MutPred		0.36		Loss of sheet (P = 0.0104);
MVP		0.12
ClinPred		0.86	D
GERP RS		3.8
Varity_R		0.26
gMVP		0.34

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: chr11-61276549;