17-39944429-G-C

Variant names:

• chr17-39944429-G-C
• NM_001195545.2:c.523G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001195545.2(LRRC3C):​c.523G>C​(p.Val175Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000746 in 1,340,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: LRRC3C NM_001195545.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.60
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32321805).

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.523G>C	p.Val175Leu	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.523G>C	p.Val175Leu	missense	Exon 4 of 4	ENSP00000367157.4	A6NJW4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.46e-7 AC: 1 AN: 1340526 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 655640

African (AFR) AF: 0.00 AC: 0 AN: 30780

American (AMR) AF: 0.00 AC: 0 AN: 31998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21966

East Asian (EAS) AF: 0.00 AC: 0 AN: 35338

South Asian (SAS) AF: 0.00 AC: 0 AN: 71570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32058

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5456

European-Non Finnish (NFE) AF: 9.48e-7 AC: 1 AN: 1055306

Other (OTH) AF: 0.00 AC: 0 AN: 56054

GnomAD4 genome Cov.: 31

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	Uncertain	0.34
BayesDel_addAF	Uncertain	0.045	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0040	T
Eigen	Benign	0.0024
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.082	D
MetaRNN	Benign	0.32	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	0.73	N
PhyloP100		2.6
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	0.49	N
REVEL	Uncertain	0.35
Sift	Benign	1.0	T
Sift4G	Benign	0.73	T
Vest4		0.48
MutPred		0.35		Gain of sheet (P = 0.0827)
MVP		0.47
ClinPred		0.42	T
GERP RS		4.7
Varity_R		0.080
gMVP		0.37

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

hg19: chr17-38100682;