Variant 16-18793388-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_015161.3(ARL6IP1):c.494-18G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000784 in 1,438,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00081 ( 0 hom. )

Consequence

ARL6IP1
NM_015161.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.976

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 16-18793388-C-A is Benign according to our data. Variant chr16-18793388-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2420894.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 linkuse as main transcript	c.494-18G>T		intron_variant		ENST00000304414.12	NP_055976.1
ARL6IP1	NM_001313858.1 linkuse as main transcript	c.407-18G>T		intron_variant			NP_001300787.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
ARL6IP1	ENST00000304414.12 linkuse as main transcript	c.494-18G>T	intron_variant	1	NM_015161.3	ENSP00000306788	P1	Q15041-1
ARL6IP1	ENST00000563861.5 linkuse as main transcript	c.*76-18G>T	intron_variant, NMD_transcript_variant	1		ENSP00000456596
ARL6IP1	ENST00000546206.6 linkuse as main transcript	c.407-18G>T	intron_variant	2		ENSP00000440048		Q15041-2
ARL6IP1	ENST00000562819.5 linkuse as main transcript	c.149-18G>T	intron_variant	5		ENSP00000457372

Frequencies

GnomAD3 genomes

AF:

0.000580

AC:

AN:

151614

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000557

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000263

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.000192

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000648

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.000709

AC:

148

AN:

208640

Hom.:

AF XY:

0.000674

AC XY:

AN XY:

114160

show subpopulations

Gnomad AFR exome

AF:

0.000346

Gnomad AMR exome

AF:

0.000132

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00158

Gnomad SAS exome

AF:

0.000604

Gnomad FIN exome

AF:

0.000492

Gnomad NFE exome

AF:

0.000868

Gnomad OTH exome

AF:

0.00106

GnomAD4 exome

AF:

0.000809

AC:

1041

AN:

1286584

Hom.:

Cov.:

AF XY:

0.000825

AC XY:

534

AN XY:

646994

show subpopulations

Gnomad4 AFR exome

AF:

0.000608

Gnomad4 AMR exome

AF:

0.000242

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00102

Gnomad4 SAS exome

AF:

0.000485

Gnomad4 FIN exome

AF:

0.000497

Gnomad4 NFE exome

AF:

0.000872

Gnomad4 OTH exome

AF:

0.00102

GnomAD4 genome

AF:

0.000573

AC:

AN:

151718

Hom.:

Cov.:

AF XY:

0.000499

AC XY:

AN XY:

74124

show subpopulations

Gnomad4 AFR

AF:

0.000556

Gnomad4 AMR

AF:

0.000263

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.00146

Gnomad4 FIN

AF:

0.000192

Gnomad4 NFE

AF:

0.000633

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.000322

Hom.:

Bravo

AF:

0.000680

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

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

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.7

DANN

Benign

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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