2-152718629-C-A

Variant names:

• chr2-152718629-C-A
• rs761845425
• NM_152522.7:c.5C>A

Variant summary

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

The NM_152522.7(ARL6IP6):​c.5C>A​(p.Ser2*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000145 in 1,376,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000015 (0 hom.)
• Consequence: ARL6IP6 NM_152522.7 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.5C>A	p.Ser2*	stop_gained	Exon 1 of 4	NP_689735.1	Q8N6S5
	ARL6IP6	NM_001371972.1		c.5C>A	p.Ser2*	stop_gained	Exon 1 of 4	NP_001358901.1	A0A8I5KQ30
	ARL6IP6	NR_146428.2		n.10C>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.5C>A	p.Ser2*	stop_gained	Exon 1 of 4	ENSP00000315357.5	Q8N6S5
	ARL6IP6	ENST00000692399.1		c.5C>A	p.Ser2*	stop_gained	Exon 1 of 3	ENSP00000510087.1	A0A8I5KU55
	ARL6IP6	ENST00000686080.1		c.5C>A	p.Ser2*	stop_gained	Exon 1 of 4	ENSP00000509648.1	A0A8I5KQ30

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1376378 Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1 AN XY: 675594

African (AFR) AF: 0.00 AC: 0 AN: 30606

American (AMR) AF: 0.00 AC: 0 AN: 32306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21078

East Asian (EAS) AF: 0.00 AC: 0 AN: 38314

South Asian (SAS) AF: 0.00 AC: 0 AN: 73140

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5174

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1069414

Other (OTH) AF: 0.00 AC: 0 AN: 56628

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	38
DANN	Uncertain	0.99
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.93	D
PhyloP100		3.7
Vest4		0.11
GERP RS		4.0
PromoterAI		-0.41	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=32/168	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs761845425; hg19: chr2-153575143;