3-26709696-A-C

Variant names:

• chr3-26709696-A-C
• NM_052953.4:c.24A>C

Variant summary

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

The NM_052953.4(LRRC3B):​c.24A>C​(p.Leu8Phe) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: LRRC3B NM_052953.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.84

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]

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=0.40449834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC3B	NM_052953.4	c.24A>C	p.Leu8Phe	missense_variant	Exon 2 of 2	ENST00000396641.7	NP_443185.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC3B	ENST00000396641.7	c.24A>C	p.Leu8Phe	missense_variant	Exon 2 of 2	1	NM_052953.4	ENSP00000379880.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.24A>C (p.L8F) alteration is located in exon 2 (coding exon 1) of the LRRC3B gene. This alteration results from a A to C substitution at nucleotide position 24, causing the leucine (L) at amino acid position 8 to be replaced by a phenylalanine (F). 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	0.086
BayesDel_addAF	Uncertain	0.054	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	T;.;.;T;T
Eigen	Benign	-0.072
Eigen_PC	Benign	-0.084
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.90	.;D;D;.;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.40	T;T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.90	L;.;.;L;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.99	N;D;N;N;N
REVEL	Benign	0.29
Sift	Pathogenic	0.0	D;D;D;D;D
Sift4G	Uncertain	0.016	D;D;D;D;D
Polyphen		0.99	D;.;.;D;D
Vest4		0.48
MutPred		0.44		Gain of catalytic residue at L8 (P = 0.0046);Gain of catalytic residue at L8 (P = 0.0046);Gain of catalytic residue at L8 (P = 0.0046);Gain of catalytic residue at L8 (P = 0.0046);Gain of catalytic residue at L8 (P = 0.0046);
MVP		0.77
MPC		1.3
ClinPred		0.48	T
GERP RS		0.90
Varity_R		0.21
gMVP		0.43

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: chr3-26751187;