Variant 3-26710314-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The ENST00000396641.7(LRRC3B):c.642C>A(p.Phe214Leu) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

LRRC3B
ENST00000396641.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.16

Variant links:

Genes affected

LRRC3B (HGNC:28105): (leucine rich repeat containing 3B) The protein encoded by this gene is a tumor suppressor, with lowered expression levels found in gastric, renal, colorectal, lung, and breast cancer tissues. The promoter of this gene is frequently hypermethylated in these cancer tissues, although the hypermethylation does not appear to be the cause of the reduced expression of this gene. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2015]

LRRC3B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.769

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LRRC3B	NM_052953.4 linkuse as main transcript	c.642C>A	p.Phe214Leu	missense_variant	2/2	ENST00000396641.7	NP_443185.1	Q96PB8A1LNH5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LRRC3B	ENST00000396641.7 linkuse as main transcript	c.642C>A	p.Phe214Leu	missense_variant	2/2	1	NM_052953.4	ENSP00000379880.2	Q96PB8
LRRC3B	ENST00000417744.5 linkuse as main transcript	c.642C>A	p.Phe214Leu	missense_variant	3/3	1		ENSP00000406370.1	Q96PB8
LRRC3B	ENST00000456208.2 linkuse as main transcript	c.642C>A	p.Phe214Leu	missense_variant	3/3	1		ENSP00000394940.2	Q96PB8
LRRC3B	ENST00000648296.1 linkuse as main transcript	n.642C>A		non_coding_transcript_exon_variant	3/5			ENSP00000497471.1	Q96PB8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250118

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135182

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000546

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1461718

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727140

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.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 12, 2024

The c.642C>A (p.F214L) alteration is located in exon 2 (coding exon 1) of the LRRC3B gene. This alteration results from a C to A substitution at nucleotide position 642, causing the phenylalanine (F) at amino acid position 214 to be replaced by a leucine (L). 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

1.0

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.95

.;.;D

M_CAP

Benign

0.019

MetaRNN

Pathogenic

0.77

D;D;D

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.3

L;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Uncertain

0.31

Sift

Benign

0.39

T;T;T

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.99

D;D;D

Vest4

0.85

MutPred

0.33

Loss of catalytic residue at F214 (P = 0.0612);Loss of catalytic residue at F214 (P = 0.0612);Loss of catalytic residue at F214 (P = 0.0612);

MVP

0.83

MPC

2.3

ClinPred

0.97

GERP RS

6.0

Varity_R

0.35

gMVP

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over