NM_052953.4:c.179G>A

Variant names:

• chr3-26709851-G-A
• rs1700705226
• NM_052953.4:c.179G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_052953.4(LRRC3B):​c.179G>A​(p.Arg60Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,834 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: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: LRRC3B NM_052953.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31699577).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052953.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC3B	NM_052953.4	MANE Select	c.179G>A	p.Arg60Lys	missense	Exon 2 of 2	NP_443185.1	Q96PB8
	LRRC3B	NM_001317808.2		c.179G>A	p.Arg60Lys	missense	Exon 2 of 2	NP_001304737.1	Q96PB8
	LRRC3B	NM_001317809.2		c.179G>A	p.Arg60Lys	missense	Exon 2 of 2	NP_001304738.1	Q96PB8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC3B	ENST00000396641.7	TSL:1 MANE Select	c.179G>A	p.Arg60Lys	missense	Exon 2 of 2	ENSP00000379880.2	Q96PB8
	LRRC3B	ENST00000417744.5	TSL:1	c.179G>A	p.Arg60Lys	missense	Exon 3 of 3	ENSP00000406370.1	Q96PB8
	LRRC3B	ENST00000456208.2	TSL:1	c.179G>A	p.Arg60Lys	missense	Exon 3 of 3	ENSP00000394940.2	Q96PB8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461834 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727220

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111980

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Benign	0.88
DEOGEN2	Benign	0.25	T
Eigen	Benign	-0.18
Eigen_PC	Benign	0.084
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	0.34	N
PhyloP100		4.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.020	N
REVEL	Uncertain	0.46
Sift	Benign	0.95	T
Sift4G	Benign	0.98	T
Polyphen		0.016	B
Vest4		0.13
MutPred		0.45		Gain of ubiquitination at R60 (P = 0.0155)
MVP		0.92
MPC		1.0
ClinPred		0.34	T
GERP RS		6.2
Varity_R		0.29
gMVP		0.41
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs1700705226; hg19: chr3-26751342; COSMIC: COSV67522091; COSMIC: COSV67522091;