12-122191466-A-T

Variant names:

• chr12-122191466-A-T
• rs11060167
• NM_001098519.2:c.988A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001098519.2(LRRC43):​c.988A>T​(p.Arg330Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LRRC43 NM_001098519.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.01
• Publications: 20 publications found

Genes affected

LRRC43 (HGNC:28562): (leucine rich repeat containing 43)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11713001).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098519.2. 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
	LRRC43	NM_001098519.2	MANE Select	c.988A>T	p.Arg330Trp	missense	Exon 6 of 12	NP_001091989.1	Q8N309-1
	LRRC43	NM_152759.5		c.433A>T	p.Arg145Trp	missense	Exon 6 of 12	NP_689972.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC43	ENST00000339777.5	TSL:5 MANE Select	c.988A>T	p.Arg330Trp	missense	Exon 6 of 12	ENSP00000344233.4	Q8N309-1
	LRRC43	ENST00000907479.1		c.988A>T	p.Arg330Trp	missense	Exon 6 of 12	ENSP00000577538.1
	LRRC43	ENST00000537729.5	TSL:5	c.433A>T	p.Arg145Trp	missense	Exon 6 of 6	ENSP00000438751.1	F5H0N3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461834 Hom.: 0 Cov.: 35 AF XY: 0.00000275 AC XY: 2 AN XY: 727222

African (AFR) AF: 0.00 AC: 0 AN: 33480

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111972

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N
PhyloP100		3.0
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.12
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.23	B
Vest4		0.13
MutPred		0.53		Gain of catalytic residue at R330 (P = 0)
MVP		0.21
MPC		0.26
ClinPred		0.36	T
GERP RS		4.3
Varity_R		0.068
gMVP		0.60
Mutation Taster		=96/4	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: rs11060167; hg19: chr12-122676013;