3-69104703-G-T

Position:

• chr3-69104703-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_006407.4(ARL6IP5):​c.*67G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,560,864 control chromosomes in the GnomAD database, including 154,562 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.49 (19123 hom., cov: 30)
  • Exomes 𝑓: 0.43 (135439 hom.)
• Consequence: ARL6IP5 NM_006407.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.94

Genes affected

ARL6IP5 (HGNC:16937): (ADP ribosylation factor like GTPase 6 interacting protein 5) Expression of this gene is affected by vitamin A. The encoded protein of this gene may be associated with the cytoskeleton. A similar protein in rats may play a role in the regulation of cell differentiation. The rat protein binds and inhibits the cell membrane glutamate transporter EAAC1. The expression of the rat gene is upregulated by retinoic acid, which results in a specific reduction in EAAC1-mediated glutamate transport. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.655 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARL6IP5	NM_006407.4	c.*67G>T		3_prime_UTR_variant	3/3	ENST00000273258.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL6IP5	ENST00000273258.4	c.*67G>T		3_prime_UTR_variant	3/3	1	NM_006407.4	P1
ARL6IP5	ENST00000478935.1	c.196-135G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73868 AN: 151558 Hom.: 19084 Cov.: 30

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.523

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.433 AC: 610416 AN: 1409186 Hom.: 135439 Cov.: 26 AF XY: 0.435 AC XY: 304598 AN XY: 700104

Gnomad4 AFR exome AF: 0.678

Gnomad4 AMR exome AF: 0.310

Gnomad4 ASJ exome AF: 0.382

Gnomad4 EAS exome AF: 0.614

Gnomad4 SAS exome AF: 0.518

Gnomad4 FIN exome AF: 0.339

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.451

GnomAD4 genome AF: 0.488 AC: 73955 AN: 151678 Hom.: 19123 Cov.: 30 AF XY: 0.485 AC XY: 35927 AN XY: 74088

Gnomad4 AFR AF: 0.662

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.523

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.465

Alfa AF: 0.434 Hom.: 29889

Bravo AF: 0.496

Asia WGS AF: 0.555 AC: 1929 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	14
DANN	Benign	0.92

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: rs7038; hg19: chr3-69153854; COSMIC: COSV56235037; COSMIC: COSV56235037;