21-44456654-G-T

Variant names:

• chr21-44456654-G-T
• rs774885245
• NM_030891.6:c.10G>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.10G>T​(p.Val4Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. V4M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: LRRC3 NM_030891.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 1 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=0.04645744).

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.10G>T	p.Val4Leu	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.10G>T	p.Val4Leu	missense	Exon 2 of 2	ENSP00000291592.4	Q9BY71
	LRRC3	ENST00000885220.1		c.10G>T	p.Val4Leu	missense	Exon 2 of 2	ENSP00000555279.1
	LRRC3	ENST00000885221.1		c.10G>T	p.Val4Leu	missense	Exon 2 of 2	ENSP00000555280.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000421 AC: 1 AN: 237358 AF XY: 0.00000776

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000919

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.93e-7 AC: 1 AN: 1442288 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 715718

African (AFR) AF: 0.00 AC: 0 AN: 33280

American (AMR) AF: 0.00 AC: 0 AN: 43980

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25402

East Asian (EAS) AF: 0.00 AC: 0 AN: 39410

South Asian (SAS) AF: 0.00 AC: 0 AN: 84490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103252

Other (OTH) AF: 0.00 AC: 0 AN: 59750

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.0030
DANN	Benign	0.66
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.046	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.4
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.30	N
REVEL	Benign	0.024
Sift	Benign	0.69	T
Sift4G	Benign	0.77	T
Polyphen		0.0	B
Vest4		0.058
MutPred		0.18		Loss of glycosylation at T3 (P = 0.08)
MVP		0.37
MPC		0.26
ClinPred		0.029	T
GERP RS		-5.9
Varity_R		0.043
gMVP		0.54
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs774885245; hg19: chr21-45876537;