16-18793431-C-CT

Position:

• chr16-18793431-C-CT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015161.3(ARL6IP1):​c.494-62_494-61insA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0355 in 605,932 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0052 (7 hom., cov: 0)
  • Exomes 𝑓: 0.045 (0 hom.)
• Consequence: ARL6IP1 NM_015161.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.236

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-18793431-C-CT is Benign according to our data. Variant chr16-18793431-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 1300711.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL6IP1	NM_015161.3	c.494-62_494-61insA		intron_variant		ENST00000304414.12	NP_055976.1
ARL6IP1	NM_001313858.1	c.407-62_407-61insA		intron_variant			NP_001300787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL6IP1	ENST00000304414.12	c.494-62_494-61insA		intron_variant		1	NM_015161.3	ENSP00000306788	P1
ARL6IP1	ENST00000563861.5	c.*76-62_*76-61insA		intron_variant, NMD_transcript_variant		1		ENSP00000456596
ARL6IP1	ENST00000546206.6	c.407-62_407-61insA		intron_variant		2		ENSP00000440048
ARL6IP1	ENST00000562819.5	c.149-62_149-61insA		intron_variant		5		ENSP00000457372

Frequencies

GnomAD3 genomes AF: 0.00517 AC: 724 AN: 140098 Hom.: 7 Cov.: 0

Gnomad AFR AF: 0.0157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00228

Gnomad ASJ AF: 0.000598

Gnomad EAS AF: 0.00103

Gnomad SAS AF: 0.00113

Gnomad FIN AF: 0.000910

Gnomad MID AF: 0.00340

Gnomad NFE AF: 0.00101

Gnomad OTH AF: 0.00420

GnomAD4 exome AF: 0.0446 AC: 20758 AN: 465850 Hom.: 0 AF XY: 0.0444 AC XY: 10771 AN XY: 242406

Gnomad4 AFR exome AF: 0.0613

Gnomad4 AMR exome AF: 0.0475

Gnomad4 ASJ exome AF: 0.0397

Gnomad4 EAS exome AF: 0.0660

Gnomad4 SAS exome AF: 0.0418

Gnomad4 FIN exome AF: 0.0320

Gnomad4 NFE exome AF: 0.0440

Gnomad4 OTH exome AF: 0.0444

GnomAD4 genome AF: 0.00518 AC: 726 AN: 140082 Hom.: 7 Cov.: 0 AF XY: 0.00496 AC XY: 335 AN XY: 67494

Gnomad4 AFR AF: 0.0157

Gnomad4 AMR AF: 0.00228

Gnomad4 ASJ AF: 0.000598

Gnomad4 EAS AF: 0.00103

Gnomad4 SAS AF: 0.00113

Gnomad4 FIN AF: 0.000910

Gnomad4 NFE AF: 0.00101

Gnomad4 OTH AF: 0.00419

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs34143424; hg19: chr16-18804753;