2-152718789-G-A

Variant names:

• chr2-152718789-G-A
• NM_152522.7:c.165G>A
• ARL6IP6 p.Leu55Leu

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152522.7(ARL6IP6):​c.165G>A​(p.Leu55Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,454,826 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ARL6IP6 NM_152522.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.239
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).

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.165G>A	p.Leu55Leu	synonymous	Exon 1 of 4	NP_689735.1	Q8N6S5
	ARL6IP6	NM_001371972.1		c.165G>A	p.Leu55Leu	synonymous	Exon 1 of 4	NP_001358901.1	A0A8I5KQ30
	ARL6IP6	NR_146428.2		n.170G>A		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6IP6	ENST00000326446.10	TSL:1 MANE Select	c.165G>A	p.Leu55Leu	synonymous	Exon 1 of 4	ENSP00000315357.5	Q8N6S5
	ARL6IP6	ENST00000692399.1		c.165G>A	p.Leu55Leu	synonymous	Exon 1 of 3	ENSP00000510087.1	A0A8I5KU55
	ARL6IP6	ENST00000686080.1		c.165G>A	p.Leu55Leu	synonymous	Exon 1 of 4	ENSP00000509648.1	A0A8I5KQ30

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454826 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 723316

African (AFR) AF: 0.00 AC: 0 AN: 33338

American (AMR) AF: 0.00 AC: 0 AN: 43466

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25958

East Asian (EAS) AF: 0.00 AC: 0 AN: 39522

South Asian (SAS) AF: 0.00 AC: 0 AN: 85196

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52928

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108706

Other (OTH) AF: 0.0000167 AC: 1 AN: 59962

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	10
DANN	Benign	0.96
PhyloP100		0.24
PromoterAI		0.050	Neutral
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.8
Mutation Taster		=100/0	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-153575303;