Variant 16-18793379-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015161.3(ARL6IP1):c.494-9T>A 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 0.0011 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 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0008291

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.64

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 541704.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL6IP1	NM_015161.3 linkuse as main transcript	c.494-9T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000304414.12	NP_055976.1
ARL6IP1	NM_001313858.1 linkuse as main transcript	c.407-9T>A		splice_polypyrimidine_tract_variant, intron_variant			NP_001300787.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ARL6IP1	ENST00000304414.12 linkuse as main transcript	c.494-9T>A	splice_polypyrimidine_tract_variant, intron_variant	1	NM_015161.3	ENSP00000306788	P1	Q15041-1
ARL6IP1	ENST00000563861.5 linkuse as main transcript	c.*76-9T>A	splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant	1		ENSP00000456596
ARL6IP1	ENST00000546206.6 linkuse as main transcript	c.407-9T>A	splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000440048		Q15041-2
ARL6IP1	ENST00000562819.5 linkuse as main transcript	c.149-9T>A	splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000457372

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

164

AN:

151666

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.000927

AC:

183

AN:

197432

Hom.:

AF XY:

0.000891

AC XY:

AN XY:

107720

show subpopulations

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 SAS 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.:

Cov.:

AF XY:

0.00103

AC XY:

681

AN XY:

661546

show subpopulations

Gnomad4 AFR exome

AF:

0.00195

Gnomad4 AMR exome

AF:

0.000365

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000131

Gnomad4 FIN exome

AF:

0.00145

Gnomad4 NFE exome

AF:

0.00124

Gnomad4 OTH exome

AF:

0.00117

GnomAD4 genome

AF:

0.00108

AC:

164

AN:

151782

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.00208

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000665

Gnomad4 NFE

AF:

0.000972

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.000894

Hom.:

Bravo

AF:

0.00115

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 61

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 19, 2023

- -

ARL6IP1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 13, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.1

DANN

Benign

0.69

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over