21-44456675-C-T

Variant names:

• chr21-44456675-C-T
• rs552887690
• NM_030891.6:c.31C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030891.6(LRRC3):​c.31C>T​(p.Leu11Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,452,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L11V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: LRRC3 NM_030891.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 0 publications found

Genes affected

LRRC3 (HGNC:14965): (leucine rich repeat containing 3) Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05199787).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030891.6. 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
	LRRC3	NM_030891.6	MANE Select	c.31C>T	p.Leu11Phe	missense	Exon 2 of 2	NP_112153.1	Q9BY71

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC3	ENST00000291592.6	TSL:1 MANE Select	c.31C>T	p.Leu11Phe	missense	Exon 2 of 2	ENSP00000291592.4	Q9BY71
	LRRC3	ENST00000885220.1		c.31C>T	p.Leu11Phe	missense	Exon 2 of 2	ENSP00000555279.1
	LRRC3	ENST00000885221.1		c.31C>T	p.Leu11Phe	missense	Exon 2 of 2	ENSP00000555280.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1452978 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722284

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25992

East Asian (EAS) AF: 0.00 AC: 0 AN: 39522

South Asian (SAS) AF: 0.00 AC: 0 AN: 85942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48858

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5756

European-Non Finnish (NFE) AF: 0.00000271 AC: 3 AN: 1108868

Other (OTH) AF: 0.00 AC: 0 AN: 60136

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.0050
DANN	Benign	0.93
DEOGEN2	Benign	0.028	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.22	T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		-2.7
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.37	N
REVEL	Benign	0.23
Sift	Benign	0.46	T
Sift4G	Benign	0.42	T
Polyphen		0.092	B
Vest4		0.030
MutPred		0.37		Loss of stability (P = 0.0467)
MVP		0.15
MPC		0.29
ClinPred		0.074	T
GERP RS		-6.2
Varity_R		0.051
gMVP		0.36
Mutation Taster		=94/6	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: rs552887690; hg19: chr21-45876558;