17-39944594-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001195545.2(LRRC3C):c.688G>A(p.Gly230Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000145 in 1,383,206 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: LRRC3C NM_001195545.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.04

Genes affected

LRRC3C (HGNC:40034): (leucine rich repeat containing 3C) Predicted to be integral component of membrane. Predicted to be active in extracellular matrix and extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC3C	NM_001195545.2	c.688G>A	p.Gly230Arg	missense_variant	4/4	ENST00000377924.6
LRRC3C	XM_017024003.1	c.688G>A	p.Gly230Arg	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC3C	ENST00000377924.6	c.688G>A	p.Gly230Arg	missense_variant	4/4	3	NM_001195545.2	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1383206 Hom.: 0 Cov.: 35 AF XY: 0.00000293 AC XY: 2 AN XY: 682502

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2023

The c.688G>A (p.G230R) alteration is located in exon 2 (coding exon 2) of the LRRC3C gene. This alteration results from a G to A substitution at nucleotide position 688, causing the glycine (G) at amino acid position 230 to be replaced by an arginine (R). 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	Pathogenic	0.90
BayesDel_addAF	Benign	-0.0075	T
BayesDel_noAF	Benign	-0.25
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.089	T
Eigen	Benign	0.023
Eigen_PC	Benign	0.024
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	0.86	D
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.30
Sift	Benign	0.14	T
Sift4G	Benign	0.20	T
Vest4		0.80
MutPred		0.54		Gain of MoRF binding (P = 0.0064);
MVP		0.59
ClinPred		0.95	D
GERP RS		3.8
Varity_R		0.17
gMVP		0.78

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

LitVar

Other links and lift over

dbSNP: rs1322121852; hg19: chr17-38100847;