17-39944653-T-G

Position:

• chr17-39944653-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001195545.2(LRRC3C):​c.747T>G​(p.Asp249Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC3C NM_001195545.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.250

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05461037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC3C	NM_001195545.2	c.747T>G	p.Asp249Glu	missense_variant	4/4	ENST00000377924.6
LRRC3C	XM_017024003.1	c.747T>G	p.Asp249Glu	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC3C	ENST00000377924.6	c.747T>G	p.Asp249Glu	missense_variant	4/4	3	NM_001195545.2	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1383722 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 682804

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Apr 19, 2023

The c.747T>G (p.D249E) alteration is located in exon 2 (coding exon 2) of the LRRC3C gene. This alteration results from a T to G substitution at nucleotide position 747, causing the aspartic acid (D) at amino acid position 249 to be replaced by a glutamic acid (E). 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	Benign	0.084
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.72
DANN	Benign	0.40
DEOGEN2	Benign	0.00053	T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.86	N
MutationTaster	Benign	0.95	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.094
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.13
MutPred		0.36		Gain of disorder (P = 0.0946);
MVP		0.15
ClinPred		0.49	T
GERP RS		-0.72
Varity_R		0.028
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr17-38100906;