NM_001006607.3:c.448C>G

Variant names:

• chr17-46513160-C-G
• rs1249441311
• NM_001006607.3:c.448C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001006607.3(LRRC37A2):​c.448C>G​(p.Leu150Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000011 (0 hom., cov: 16)
  • Exomes 𝑓: 0.000049 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A2 NM_001006607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0840
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.104201555).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006607.3. 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
	LRRC37A2	NM_001006607.3	MANE Select	c.448C>G	p.Leu150Val	missense	Exon 1 of 14	NP_001006608.2	A6NM11
	LRRC37A2	NM_001385803.1		c.448C>G	p.Leu150Val	missense	Exon 1 of 14	NP_001372732.1
	ARL17A	NM_001288812.1		c.*21+3934G>C		intron	N/A	NP_001275741.1	Q8IVW1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LRRC37A2	ENST00000576629.6	TSL:5 MANE Select	c.448C>G	p.Leu150Val	missense	Exon 1 of 14	ENSP00000459551.1	A6NM11
	LRRC37A2	ENST00000706058.1		c.448C>G	p.Leu150Val	missense	Exon 1 of 8	ENSP00000516210.1	A0A994J7J8
	LRRC37A2	ENST00000705813.1		c.-89+1552C>G		intron	N/A	ENSP00000516171.1	A0A994J7H6

Frequencies

GnomAD3 genomes AF: 0.0000112 AC: 1 AN: 89684 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000342

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000493 AC: 35 AN: 710526 Hom.: 0 Cov.: 5 AF XY: 0.0000430 AC XY: 15 AN XY: 349240

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31294

American (AMR) AF: 0.00 AC: 0 AN: 32266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10280

East Asian (EAS) AF: 0.00 AC: 0 AN: 35124

South Asian (SAS) AF: 0.00 AC: 0 AN: 36786

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33324

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1840

European-Non Finnish (NFE) AF: 0.0000682 AC: 34 AN: 498206

Other (OTH) AF: 0.0000318 AC: 1 AN: 31406

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000112 AC: 1 AN: 89684 Hom.: 0 Cov.: 16 AF XY: 0.00 AC XY: 0 AN XY: 44284

African (AFR) AF: 0.00 AC: 0 AN: 35568

American (AMR) AF: 0.00 AC: 0 AN: 8866

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1374

East Asian (EAS) AF: 0.00 AC: 0 AN: 4296

South Asian (SAS) AF: 0.00 AC: 0 AN: 2088

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 102

European-Non Finnish (NFE) AF: 0.0000342 AC: 1 AN: 29276

Other (OTH) AF: 0.00 AC: 0 AN: 1070

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions as Germline

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	Benign	0.11
BayesDel_addAF	Benign	-0.0013	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	6.0
DANN	Benign	0.89
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.88
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.084
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.15	T
Polyphen		0.35	B
Vest4		0.24
MutPred		0.19		Loss of stability (P = 0.0672)
MVP		0.099
ClinPred		0.12	T
GERP RS		0.77
Varity_R		0.068
gMVP		0.020

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: rs1249441311; hg19: chr17-44590526;