chr3-69101972-G-A

Position:

• chr3-69101972-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000273258.4(ARL6IP5):​c.310G>A​(p.Val104Met) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ARL6IP5 ENST00000273258.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.63

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35099372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARL6IP5	NM_006407.4	c.310G>A	p.Val104Met	missense_variant	2/3	ENST00000273258.4	NP_006398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARL6IP5	ENST00000273258.4	c.310G>A	p.Val104Met	missense_variant	2/3	1	NM_006407.4	ENSP00000273258	P1
ARL6IP5	ENST00000478935.1	c.195+115G>A		intron_variant		1		ENSP00000420138
ARL6IP5	ENST00000470936.1	n.322G>A		non_coding_transcript_exon_variant	2/2	2
ARL6IP5	ENST00000484921.1	c.*126G>A		3_prime_UTR_variant, NMD_transcript_variant	3/4	5		ENSP00000419374

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2024

The c.310G>A (p.V104M) alteration is located in exon 2 (coding exon 2) of the ARL6IP5 gene. This alteration results from a G to A substitution at nucleotide position 310, causing the valine (V) at amino acid position 104 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.092	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	0.59	D;D
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.50	N
REVEL	Uncertain	0.33
Sift	Benign	0.055	T
Sift4G	Benign	0.22	T
Polyphen		0.89	P
Vest4		0.21
MutPred		0.57		Gain of MoRF binding (P = 0.1001);
MVP		0.76
MPC		0.19
ClinPred		0.64	D
GERP RS		4.9
Varity_R		0.077
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-69151123;