rs1288229533

Variant names:

• chr17-46297522-C-G
• rs1288229533
• NM_014834.4:c.2389C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_014834.4(LRRC37A):​c.2389C>G​(p.Leu797Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 7)
  • Exomes 𝑓: 0.000031 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A NM_014834.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.55
• Publications: 0 publications found

Genes affected

LRRC37A (HGNC:29069): (leucine rich repeat containing 37A) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ARL17B (HGNC:32387): (ADP ribosylation factor like GTPase 17B) 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

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.01267764).
• BP6: Variant 17-46297522-C-G is Benign according to our data. Variant chr17-46297522-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3539978.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014834.4. 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
	LRRC37A	NM_014834.4	MANE Select	c.2389C>G	p.Leu797Val	missense	Exon 1 of 14	NP_055649.4	A6NMS7
	ARL17B	NM_001103154.2		c.*21+2004G>C		intron	N/A	NP_001096624.1
	ARL17B	NM_001352769.1		c.*21+2004G>C		intron	N/A	NP_001339698.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC37A	ENST00000320254.5	TSL:1 MANE Select	c.2389C>G	p.Leu797Val	missense	Exon 1 of 14	ENSP00000326324.5	A6NMS7
	LRRC37A	ENST00000393465.7	TSL:5	c.2389C>G	p.Leu797Val	missense	Exon 1 of 12	ENSP00000377108.2	A8MUI5
	LRRC37A	ENST00000496930.5	TSL:2	c.-277-2272C>G		intron	N/A	ENSP00000437021.1	E9PP10

Frequencies

GnomAD3 genomes Cov.: 7

GnomAD2 exomes AF: 0.00402 AC: 2 AN: 498 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 1.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000307 AC: 16 AN: 521888 Hom.: 3 Cov.: 5 AF XY: 0.0000352 AC XY: 10 AN XY: 284218

African (AFR) AF: 0.00 AC: 0 AN: 16008

American (AMR) AF: 0.00 AC: 0 AN: 24722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17798

East Asian (EAS) AF: 0.000756 AC: 14 AN: 18530

South Asian (SAS) AF: 0.00 AC: 0 AN: 58620

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2272

European-Non Finnish (NFE) AF: 0.00000636 AC: 2 AN: 314488

Other (OTH) AF: 0.00 AC: 0 AN: 28422

GnomAD4 genome Cov.: 7

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.10
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.063
DANN	Benign	0.34
DEOGEN2	Benign	0.0082	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
PhyloP100		-3.5
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.023
Sift	Benign	0.28	T
Sift4G	Benign	0.23	T
Polyphen		0.039	B
Vest4		0.050
MutPred		0.24		Loss of catalytic residue at L797 (P = 0.0319)
MVP		0.043
ClinPred		0.026	T
GERP RS		-1.8
Varity_R		0.045
gMVP		0.046
Mutation Taster		=100/0	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: rs1288229533; hg19: chr17-44374888;