rs550252059

Variant names:

• chr17-46515041-C-A
• rs550252059
• NM_001006607.3:c.2329C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-46515041-C-A
• chr17-46515041-C-T

Variant summary

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

The NM_001006607.3(LRRC37A2):​c.2329C>A​(p.Pro777Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 6)
  • Exomes 𝑓: 0.0000072 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: LRRC37A2 NM_001006607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0220
• 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=0.13499948).

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.2329C>A	p.Pro777Thr	missense	Exon 1 of 14	NP_001006608.2	A6NM11
	LRRC37A2	NM_001385803.1		c.2329C>A	p.Pro777Thr	missense	Exon 1 of 14	NP_001372732.1
	ARL17A	NM_001288812.1		c.*21+2053G>T		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.2329C>A	p.Pro777Thr	missense	Exon 1 of 14	ENSP00000459551.1	A6NM11
	LRRC37A2	ENST00000706058.1		c.2329C>A	p.Pro777Thr	missense	Exon 1 of 8	ENSP00000516210.1	A0A994J7J8
	LRRC37A2	ENST00000705813.1		c.-88-2321C>A		intron	N/A	ENSP00000516171.1	A0A994J7H6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 71922 Hom.: 0 Cov.: 6

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000722 AC: 5 AN: 692428 Hom.: 2 Cov.: 4 AF XY: 0.00000293 AC XY: 1 AN XY: 341130

African (AFR) AF: 0.000136 AC: 3 AN: 22138

American (AMR) AF: 0.00 AC: 0 AN: 30360

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10060

East Asian (EAS) AF: 0.00 AC: 0 AN: 33558

South Asian (SAS) AF: 0.00 AC: 0 AN: 36122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1558

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 495890

Other (OTH) AF: 0.0000683 AC: 2 AN: 29274

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 71922 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 35622

African (AFR) AF: 0.00 AC: 0 AN: 21836

American (AMR) AF: 0.00 AC: 0 AN: 7418

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1274

East Asian (EAS) AF: 0.00 AC: 0 AN: 4014

South Asian (SAS) AF: 0.00 AC: 0 AN: 1810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6266

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 100

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 27920

Other (OTH) AF: 0.00 AC: 0 AN: 844

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	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	2.9
DANN	Benign	0.88
DEOGEN2	Benign	0.079	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.022
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.076
Sift	Uncertain	0.0040	D
Sift4G	Benign	0.078	T
Polyphen		0.27	B
Vest4		0.24
MutPred		0.26		Gain of phosphorylation at P777 (P = 0.0062)
MVP		0.040
ClinPred		0.22	T
GERP RS		-1.8
Varity_R		0.097
gMVP		0.12

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: rs550252059; hg19: chr17-44592407;