16-18793089-T-C

Position:

• chr16-18793089-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015161.3(ARL6IP1):​c.*163A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0966 in 547,234 control chromosomes in the GnomAD database, including 2,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (767 hom., cov: 33)
  • Exomes 𝑓: 0.096 (2122 hom.)
• Consequence: ARL6IP1 NM_015161.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.22

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 16-18793089-T-C is Benign according to our data. Variant chr16-18793089-T-C is described in ClinVar as [Benign]. Clinvar id is 1231012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL6IP1	NM_015161.3	c.*163A>G		3_prime_UTR_variant	6/6	ENST00000304414.12	NP_055976.1
ARL6IP1	NM_001313858.1	c.*163A>G		3_prime_UTR_variant	6/6		NP_001300787.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL6IP1	ENST00000304414.12	c.*163A>G		3_prime_UTR_variant	6/6	1	NM_015161.3	ENSP00000306788	P1
ARL6IP1	ENST00000563861.5	c.*357A>G		3_prime_UTR_variant, NMD_transcript_variant	5/5	1		ENSP00000456596
ARL6IP1	ENST00000546206.6	c.*163A>G		3_prime_UTR_variant	6/6	2		ENSP00000440048
ARL6IP1	ENST00000562819.5	c.*163A>G		3_prime_UTR_variant	3/3	5		ENSP00000457372

Frequencies

GnomAD3 genomes AF: 0.0975 AC: 14836 AN: 152166 Hom.: 769 Cov.: 33

Gnomad AFR AF: 0.0843

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0781

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.0885

Gnomad OTH AF: 0.121

GnomAD4 exome AF: 0.0962 AC: 37999 AN: 394950 Hom.: 2122 Cov.: 4 AF XY: 0.0984 AC XY: 20756 AN XY: 210962

Gnomad4 AFR exome AF: 0.0869

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.0790

Gnomad4 SAS exome AF: 0.134

Gnomad4 FIN exome AF: 0.0715

Gnomad4 NFE exome AF: 0.0879

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.0975 AC: 14846 AN: 152284 Hom.: 767 Cov.: 33 AF XY: 0.100 AC XY: 7475 AN XY: 74466

Gnomad4 AFR AF: 0.0843

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.0781

Gnomad4 NFE AF: 0.0885

Gnomad4 OTH AF: 0.124

Alfa AF: 0.0937 Hom.: 712

Bravo AF: 0.100

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.48
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11540998; hg19: chr16-18804411;