2-152718958-C-A

Position:

• chr2-152718958-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152522.7(ARL6IP6):​c.334C>A​(p.Leu112Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARL6IP6 NM_152522.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.108

Genes affected

ARL6IP6 (HGNC:24048): (ADP ribosylation factor like GTPase 6 interacting protein 6) Predicted to be located in nuclear inner membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11423108).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARL6IP6	NM_152522.7	c.334C>A	p.Leu112Ile	missense_variant	1/4	ENST00000326446.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL6IP6	ENST00000326446.10	c.334C>A	p.Leu112Ile	missense_variant	1/4	1	NM_152522.7	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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 18, 2023

The c.334C>A (p.L112I) alteration is located in exon 1 (coding exon 1) of the ARL6IP6 gene. This alteration results from a C to A substitution at nucleotide position 334, causing the leucine (L) at amino acid position 112 to be replaced by an isoleucine (I). 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	0.083
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.72	N
REVEL	Benign	0.030
Sift	Uncertain	0.024	D
Sift4G	Uncertain	0.042	D
Polyphen		0.22	B
Vest4		0.28
MutPred		0.27		Loss of catalytic residue at L112 (P = 0.1253);
MVP		0.33
MPC		0.24
ClinPred		0.18	T
GERP RS		0.71
Varity_R		0.082
gMVP		0.20

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: chr2-153575472;