17-46513311-G-A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2 BP4_Strong

The NM_001006607.3(LRRC37A2):c.599G>A(p.Arg200Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00068 (0 hom., cov: 5)
  • Exomes 𝑓: 0.00017 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A2 NM_001006607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.55

Genes affected

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARL17A (HGNC:24096): (ADP ribosylation factor like GTPase 17A) Predicted to enable GTP binding activity. Predicted to be involved in intracellular protein transport and vesicle-mediated transport. Predicted to be located in Golgi apparatus. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PP2: Missense variant where missense usually causes diseases, LRRC37A2
• BP4: Computational evidence support a benign effect (MetaRNN=0.02721712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LRRC37A2	NM_001006607.3	c.599G>A	p.Arg200Gln	missense_variant	1/14	ENST00000576629.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LRRC37A2	ENST00000576629.6	c.599G>A	p.Arg200Gln	missense_variant	1/14	5	NM_001006607.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 38 AN: 55680 Hom.: 0 Cov.: 5 FAILED QC

Gnomad AFR AF: 0.00177

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000194

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000500

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000172 AC: 107 AN: 622780 Hom.: 4 Cov.: 3 AF XY: 0.000155 AC XY: 48 AN XY: 308794

Gnomad4 AFR exome AF: 0.000734

Gnomad4 AMR exome AF: 0.000256

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000289

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000158

Gnomad4 OTH exome AF: 0.000433

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000681 AC: 38 AN: 55798 Hom.: 0 Cov.: 5 AF XY: 0.000552 AC XY: 15 AN XY: 27184

Gnomad4 AFR AF: 0.00176

Gnomad4 AMR AF: 0.000193

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000500

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000422 Hom.: 0

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

Oct 05, 2021

The c.599G>A (p.R200Q) alteration is located in exon 1 (coding exon 1) of the LRRC37A2 gene. This alteration results from a G to A substitution at nucleotide position 599, causing the arginine (R) at amino acid position 200 to be replaced by a glutamine (Q). 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	0.073
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	0.30
Dann	Benign	0.43
DEOGEN2	Benign	0.00047	T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00086	N
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.027	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.33	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.59	T
Sift4G	Benign	0.66	T;T
Polyphen		0.0020	B;B
Vest4		0.057
MutPred		0.17		Loss of ubiquitination at K202 (P = 0.1459);Loss of ubiquitination at K202 (P = 0.1459);
MVP		0.040
ClinPred		0.0073	T
GERP RS		-4.4
Varity_R		0.018
gMVP		0.023

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: rs1280064300; hg19: chr17-44590677;