rs187822079

Variant names:

• chr16-18793379-A-T
• rs187822079
• NM_015161.3:c.494-9T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_015161.3(ARL6IP1):​c.494-9T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,472,622 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (2 hom.)
• Consequence: ARL6IP1 NM_015161.3 intron
• Scores: Splicing: ADA: 0.0008291
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.64
• Publications: 0 publications found

Genes affected

ARL6IP1 (HGNC:697): (ADP ribosylation factor like GTPase 6 interacting protein 1) This gene belongs to the ARL6ip family and encodes a transmembrane protein that is predominantly localized to intracytoplasmic membranes. It is highly expressed in early myeloid progenitor cells and thought to be involved in protein transport, membrane trafficking, or cell signaling during hematopoietic maturation. Mutations in this gene are associated with spastic paraplegia 61 (SPG61). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2015]

ARL6IP1 Gene-Disease associations (from GenCC):

• hereditary spastic paraplegia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• hereditary spastic paraplegia 61

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000260342 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 16-18793379-A-T is Benign according to our data. Variant chr16-18793379-A-T is described in ClinVar as Likely_benign. ClinVar VariationId is 541704.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015161.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6IP1	NM_015161.3	MANE Select	c.494-9T>A		intron	N/A	NP_055976.1
	ARL6IP1	NM_001313858.1		c.407-9T>A		intron	N/A	NP_001300787.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6IP1	ENST00000304414.12	TSL:1 MANE Select	c.494-9T>A		intron	N/A	ENSP00000306788.7
	ENSG00000260342	ENST00000567078.2	TSL:3	c.493+1220T>A		intron	N/A	ENSP00000454746.2
	ARL6IP1	ENST00000563861.5	TSL:1	n.*76-9T>A		intron	N/A	ENSP00000456596.1

Frequencies

GnomAD3 genomes AF: 0.00108 AC: 164 AN: 151666 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00208

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000665

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000972

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000927 AC: 183 AN: 197432 AF XY: 0.000891

Gnomad AFR exome AF: 0.00173

Gnomad AMR exome AF: 0.000333

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00127

Gnomad NFE exome AF: 0.00130

Gnomad OTH exome AF: 0.000678

GnomAD4 exome AF: 0.00111 AC: 1463 AN: 1320840 Hom.: 2 Cov.: 21 AF XY: 0.00103 AC XY: 681 AN XY: 661546

African (AFR) AF: 0.00195 AC: 56 AN: 28702

American (AMR) AF: 0.000365 AC: 12 AN: 32856

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23200

East Asian (EAS) AF: 0.00 AC: 0 AN: 38032

South Asian (SAS) AF: 0.0000131 AC: 1 AN: 76278

European-Finnish (FIN) AF: 0.00145 AC: 75 AN: 51836

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4702

European-Non Finnish (NFE) AF: 0.00124 AC: 1255 AN: 1010514

Other (OTH) AF: 0.00117 AC: 64 AN: 54720

GnomAD4 genome AF: 0.00108 AC: 164 AN: 151782 Hom.: 0 Cov.: 33 AF XY: 0.00102 AC XY: 76 AN XY: 74216

African (AFR) AF: 0.00208 AC: 86 AN: 41384

American (AMR) AF: 0.000263 AC: 4 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.000665 AC: 7 AN: 10520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000972 AC: 66 AN: 67900

Other (OTH) AF: 0.000476 AC: 1 AN: 2102

Alfa AF: 0.000894 Hom.: 0

Bravo AF: 0.00115

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	ARL6IP1-related disorder (1)
-	-	1	Hereditary spastic paraplegia 61 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.1
DANN	Benign	0.69
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00083
dbscSNV1_RF	Benign	0.12
SpliceAI score (max)		0.030		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: rs187822079; hg19: chr16-18804701;