chr2-152718965-C-T

Variant names:

• chr2-152718965-C-T
• rs1699498035
• NM_152522.7:c.341C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001350068.2(ARL6IP6):​c.-420C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,447,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ARL6IP6 NM_001350068.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38867328).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001350068.2. 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.341C>T	p.Ser114Leu	missense	Exon 1 of 4	NP_689735.1	Q8N6S5
	ARL6IP6	NM_001350068.2		c.-420C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	NP_001336997.1
	ARL6IP6	NM_001371972.1		c.341C>T	p.Ser114Leu	missense	Exon 1 of 4	NP_001358901.1	A0A8I5KQ30

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARL6IP6	ENST00000326446.10	TSL:1 MANE Select	c.341C>T	p.Ser114Leu	missense	Exon 1 of 4	ENSP00000315357.5	Q8N6S5
	ARL6IP6	ENST00000692399.1		c.341C>T	p.Ser114Leu	missense	Exon 1 of 3	ENSP00000510087.1	A0A8I5KU55
	ARL6IP6	ENST00000686080.1		c.341C>T	p.Ser114Leu	missense	Exon 1 of 4	ENSP00000509648.1	A0A8I5KQ30

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1447350 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718392

African (AFR) AF: 0.00 AC: 0 AN: 32930

American (AMR) AF: 0.00 AC: 0 AN: 42516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25736

East Asian (EAS) AF: 0.00 AC: 0 AN: 39192

South Asian (SAS) AF: 0.00 AC: 0 AN: 84296

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53174

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1104036

Other (OTH) AF: 0.0000167 AC: 1 AN: 59760

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.063	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.4
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.15
Sift	Uncertain	0.014	D
Sift4G	Benign	0.064	T
Polyphen		0.69	P
Vest4		0.56
MutPred		0.39		Gain of catalytic residue at S114 (P = 0.1244)
MVP		0.56
MPC		0.54
ClinPred		0.96	D
GERP RS		4.7
PromoterAI		-0.0017	Neutral
Varity_R		0.33
gMVP		0.58
Mutation Taster		=82/18	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

Other links and lift over

dbSNP: rs1699498035; hg19: chr2-153575479; COSMIC: COSV58442922; COSMIC: COSV58442922;