NM_015161.3:c.494-62delA

Variant names:

• chr16-18793431-CT-C
• rs34143424
• NM_015161.3:c.494-62delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015161.3(ARL6IP1):​c.494-62delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 602,714 control chromosomes in the GnomAD database, including 8,171 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (7186 hom., cov: 0)
  • Exomes 𝑓: 0.35 (985 hom.)
• Consequence: ARL6IP1 NM_015161.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.236
• Publications: 2 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.

• BP6: Variant 16-18793431-CT-C is Benign according to our data. Variant chr16-18793431-CT-C is described in ClinVar as Benign. ClinVar VariationId is 1262023.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6IP1	NM_015161.3	MANE Select	c.494-62delA		intron	N/A	NP_055976.1	Q15041-1
	ARL6IP1	NM_001313858.1		c.407-62delA		intron	N/A	NP_001300787.1	Q15041-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6IP1	ENST00000304414.12	TSL:1 MANE Select	c.494-62delA		intron	N/A	ENSP00000306788.7	Q15041-1
	ENSG00000260342	ENST00000567078.2	TSL:3	c.493+1167delA		intron	N/A	ENSP00000454746.2	H3BN98
	ARL6IP1	ENST00000563861.5	TSL:1	n.*76-62delA		intron	N/A	ENSP00000456596.1	H3BS91

Frequencies

GnomAD3 genomes AF: 0.324 AC: 45387 AN: 139966 Hom.: 7184 Cov.: 0

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.376

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.373

Gnomad OTH AF: 0.340

GnomAD4 exome AF: 0.355 AC: 164230 AN: 462764 Hom.: 985 AF XY: 0.354 AC XY: 85214 AN XY: 240606

African (AFR) AF: 0.331 AC: 3376 AN: 10202

American (AMR) AF: 0.333 AC: 3752 AN: 11272

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 3719 AN: 10338

East Asian (EAS) AF: 0.314 AC: 6729 AN: 21442

South Asian (SAS) AF: 0.337 AC: 11705 AN: 34780

European-Finnish (FIN) AF: 0.353 AC: 9762 AN: 27664

Middle Eastern (MID) AF: 0.353 AC: 603 AN: 1708

European-Non Finnish (NFE) AF: 0.361 AC: 116530 AN: 322698

Other (OTH) AF: 0.355 AC: 8054 AN: 22660

GnomAD4 genome AF: 0.324 AC: 45391 AN: 139950 Hom.: 7186 Cov.: 0 AF XY: 0.322 AC XY: 21681 AN XY: 67424

African (AFR) AF: 0.257 AC: 9818 AN: 38214

American (AMR) AF: 0.315 AC: 4421 AN: 14024

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 1257 AN: 3340

East Asian (EAS) AF: 0.111 AC: 539 AN: 4844

South Asian (SAS) AF: 0.306 AC: 1348 AN: 4404

European-Finnish (FIN) AF: 0.370 AC: 2846 AN: 7682

Middle Eastern (MID) AF: 0.325 AC: 87 AN: 268

European-Non Finnish (NFE) AF: 0.373 AC: 24005 AN: 64382

Other (OTH) AF: 0.341 AC: 650 AN: 1906

Alfa AF: 0.135 Hom.: 222

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

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: rs34143424; hg19: chr16-18804753;