2-152718965-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152522.7(ARL6IP6):c.341C>T(p.Ser114Leu) variant causes a missense 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_152522.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.44

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 1 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARL6IP6	NM_152522.7	c.341C>T	p.Ser114Leu	missense_variant	1/4	ENST00000326446.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARL6IP6	ENST00000326446.10	c.341C>T	p.Ser114Leu	missense_variant	1/4	1	NM_152522.7	P1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000167

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Aug 25, 2020

- -

Computational scores

Source: dbNSFP v4.3

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
MutationTaster	Benign	0.99	D
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
Varity_R		0.33
gMVP		0.58

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

LitVar

Other links and lift over

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