rs546167542

Variant names:

• chr17-39944481-G-A
• rs546167542
• NM_001195545.2:c.575G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-39944481-G-A
• chr17-39944481-G-T
• chr17-39944481-G-C

Variant summary

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

The NM_001195545.2(LRRC3C):​c.575G>A​(p.Arg192Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,487,326 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R192L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: LRRC3C NM_001195545.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.34
• Publications: 1 publications found

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

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=0.06244126).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195545.2. 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
	LRRC3C	NM_001195545.2	MANE Select	c.575G>A	p.Arg192Gln	missense	Exon 4 of 4	NP_001182474.1	A6NJW4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC3C	ENST00000377924.6	TSL:3 MANE Select	c.575G>A	p.Arg192Gln	missense	Exon 4 of 4	ENSP00000367157.4	A6NJW4

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151948 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000624 AC: 6 AN: 96092 AF XY: 0.0000400

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000965

Gnomad ASJ exome AF: 0.000228

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000562

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000157 AC: 21 AN: 1335378 Hom.: 0 Cov.: 40 AF XY: 0.0000169 AC XY: 11 AN XY: 652516

African (AFR) AF: 0.00 AC: 0 AN: 30704

American (AMR) AF: 0.000126 AC: 4 AN: 31762

Ashkenazi Jewish (ASJ) AF: 0.0000463 AC: 1 AN: 21580

East Asian (EAS) AF: 0.0000566 AC: 2 AN: 35326

South Asian (SAS) AF: 0.0000284 AC: 2 AN: 70528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31454

Middle Eastern (MID) AF: 0.000184 AC: 1 AN: 5440

European-Non Finnish (NFE) AF: 0.00000760 AC: 8 AN: 1052754

Other (OTH) AF: 0.0000537 AC: 3 AN: 55830

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151948 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 74204

African (AFR) AF: 0.00 AC: 0 AN: 41382

American (AMR) AF: 0.0000655 AC: 1 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

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	0.089
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	12
DANN	Benign	0.68
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.75	N
PhyloP100		2.3
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.056
Sift	Benign	0.80	T
Sift4G	Benign	0.71	T
Vest4		0.22
MutPred		0.51		Gain of helix (P = 0.132)
MVP		0.15
ClinPred		0.030	T
GERP RS		3.7
Varity_R		0.032
gMVP		0.40
Mutation Taster		=84/16	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: rs546167542; hg19: chr17-38100734;