11-61509433-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001145077.2(LRRC10B):​c.435C>A​(p.Asp145Glu) 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. 12/20 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)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

LRRC10B
NM_001145077.2 missense

Scores

3
1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.17
Variant links:
Genes affected
LRRC10B (HGNC:37215): (leucine rich repeat containing 10B)

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.21245822).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LRRC10BNM_001145077.2 linkc.435C>A p.Asp145Glu missense_variant Exon 1 of 1 ENST00000378075.4 NP_001138549.1 A6NIK2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LRRC10BENST00000378075.4 linkc.435C>A p.Asp145Glu missense_variant Exon 1 of 1 6 NM_001145077.2 ENSP00000367315.2 A6NIK2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1329300
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
654118
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Apr 13, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.435C>A (p.D145E) alteration is located in exon 1 (coding exon 1) of the LRRC10B gene. This alteration results from a C to A substitution at nucleotide position 435, causing the aspartic acid (D) at amino acid position 145 to be replaced by a glutamic acid (E). 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
Pathogenic
0.94
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.030
T
Eigen
Benign
-0.29
Eigen_PC
Benign
-0.18
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.75
T
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L
PrimateAI
Pathogenic
0.92
D
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.098
Sift
Benign
0.063
T
Sift4G
Benign
0.16
T
Polyphen
0.11
B
Vest4
0.35
MutPred
0.33
Gain of disorder (P = 0.0699);
MVP
0.048
ClinPred
0.87
D
GERP RS
3.2
Varity_R
0.35
gMVP
0.31

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: chr11-61276905; API