chr17-39944547-G-C

Variant names:

• chr17-39944547-G-C
• NM_001195545.2:c.641G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001195545.2(LRRC3C):​c.641G>C​(p.Trp214Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000732 in 1,366,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: LRRC3C NM_001195545.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09107104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LRRC3C	NM_001195545.2	c.641G>C	p.Trp214Ser	missense_variant	Exon 4 of 4	ENST00000377924.6	NP_001182474.1
LRRC3C	XM_017024003.1	c.641G>C	p.Trp214Ser	missense_variant	Exon 4 of 4		XP_016879492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LRRC3C	ENST00000377924.6	c.641G>C	p.Trp214Ser	missense_variant	Exon 4 of 4	3	NM_001195545.2	ENSP00000367157.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.32e-7 AC: 1 AN: 1366406 Hom.: 0 Cov.: 48 AF XY: 0.00 AC XY: 0 AN XY: 672342

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000281

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	1.9
DANN	Benign	0.47
DEOGEN2	Benign	0.00058	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.10	N
REVEL	Benign	0.025
Sift	Benign	0.43	T
Sift4G	Benign	0.33	T
Vest4		0.24
MutPred		0.50		Gain of disorder (P = 3e-04);
MVP		0.41
ClinPred		0.018	T
GERP RS		-2.5
Varity_R		0.055
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-38100800;