chr2-152718985-C-A

Variant names:

• chr2-152718985-C-A
• rs1699503601
• NM_152522.7:c.361C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_152522.7(ARL6IP6):​c.361C>A​(p.Leu121Ile) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARL6IP6 NM_152522.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.08
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22103855).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152522.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6IP6	NM_152522.7	MANE Select	c.361C>A	p.Leu121Ile	missense	Exon 1 of 4	NP_689735.1	Q8N6S5
	ARL6IP6	NM_001371972.1		c.361C>A	p.Leu121Ile	missense	Exon 1 of 4	NP_001358901.1	A0A8I5KQ30
	ARL6IP6	NM_001350068.2		c.-400C>A		5_prime_UTR	Exon 1 of 4	NP_001336997.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6IP6	ENST00000326446.10	TSL:1 MANE Select	c.361C>A	p.Leu121Ile	missense	Exon 1 of 4	ENSP00000315357.5	Q8N6S5
	ARL6IP6	ENST00000692399.1		c.361C>A	p.Leu121Ile	missense	Exon 1 of 3	ENSP00000510087.1	A0A8I5KU55
	ARL6IP6	ENST00000686080.1		c.361C>A	p.Leu121Ile	missense	Exon 1 of 4	ENSP00000509648.1	A0A8I5KQ30

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	20
DANN	Benign	0.81
DEOGEN2	Benign	0.028	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.9	L
PhyloP100		1.1
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.82	N
REVEL	Benign	0.056
Sift	Benign	0.069	T
Sift4G	Benign	0.16	T
Polyphen		0.70	P
Vest4		0.41
MutPred		0.34		Gain of catalytic residue at L121 (P = 0.0373)
MVP		0.56
MPC		0.50
ClinPred		0.30	T
GERP RS		1.8
PromoterAI		-0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.078
gMVP		0.19
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1699503601; hg19: chr2-153575499;