16-18793378-T-TA

Position:

• chr16-18793378-T-TA

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The ENST00000304414.12(ARL6IP1):​c.494-9_494-8insT variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000666 in 1,477,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00073 (0 hom.)
• Consequence: ARL6IP1 ENST00000304414.12 splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.64

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 16-18793378-T-TA is Benign according to our data. Variant chr16-18793378-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 706245.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL6IP1	NM_015161.3	c.494-9_494-8insT		splice_polypyrimidine_tract_variant, intron_variant		ENST00000304414.12	NP_055976.1
ARL6IP1	NM_001313858.1	c.407-9_407-8insT		splice_polypyrimidine_tract_variant, intron_variant			NP_001300787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL6IP1	ENST00000304414.12	c.494-9_494-8insT		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015161.3	ENSP00000306788	P1
ARL6IP1	ENST00000563861.5	c.*76-9_*76-8insT		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		1		ENSP00000456596
ARL6IP1	ENST00000546206.6	c.407-9_407-8insT		splice_polypyrimidine_tract_variant, intron_variant		2		ENSP00000440048
ARL6IP1	ENST00000562819.5	c.149-9_149-8insT		splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000457372

Frequencies

GnomAD3 genomes AF: 0.000123 AC: 18 AN: 146316 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000680

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000197

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000752

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000725 AC: 966 AN: 1331544 Hom.: 0 Cov.: 21 AF XY: 0.000714 AC XY: 475 AN XY: 665212

Gnomad4 AFR exome AF: 0.00118

Gnomad4 AMR exome AF: 0.00147

Gnomad4 ASJ exome AF: 0.000520

Gnomad4 EAS exome AF: 0.000530

Gnomad4 SAS exome AF: 0.000765

Gnomad4 FIN exome AF: 0.000256

Gnomad4 NFE exome AF: 0.000717

Gnomad4 OTH exome AF: 0.000784

GnomAD4 genome AF: 0.000123 AC: 18 AN: 146350 Hom.: 0 Cov.: 33 AF XY: 0.0000562 AC XY: 4 AN XY: 71178

Gnomad4 AFR AF: 0.000275

Gnomad4 AMR AF: 0.0000679

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000198

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000752

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary spastic paraplegia 61 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 26, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs748985230; hg19: chr16-18804700;