11-118581327-A-G

Variant names:

• chr11-118581327-A-G
• NM_001655.5:c.85A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001655.5(ARCN1):​c.85A>G​(p.Ile29Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARCN1 NM_001655.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.63

Genes affected

ARCN1 (HGNC:649): (archain 1) This gene maps in a region, which include the mixed lineage leukemia and Friend leukemia virus integration 1 genes, where multiple disease-associated chromosome translocations occur. It is an intracellular protein. Archain sequences are well conserved among eukaryotes and this protein may play a fundamental role in eukaryotic cell biology. It has similarities to heat shock proteins and clathrin-associated proteins, and may be involved in vesicle structure or trafficking. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15404892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARCN1	NM_001655.5	c.85A>G	p.Ile29Val	missense_variant	Exon 2 of 10	ENST00000264028.5	NP_001646.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARCN1	ENST00000264028.5	c.85A>G	p.Ile29Val	missense_variant	Exon 2 of 10	1	NM_001655.5	ENSP00000264028.4
ARCN1	ENST00000359415.8	c.208A>G	p.Ile70Val	missense_variant	Exon 3 of 11	1		ENSP00000352385.4
ARCN1	ENST00000534182.2	c.85A>G	p.Ile29Val	missense_variant	Exon 2 of 3	5		ENSP00000431676.1
ARCN1	ENST00000392859.7	c.4-1852A>G		intron_variant	Intron 1 of 8	2		ENSP00000376599.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Aug 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.85A>G (p.I29V) alteration is located in exon 2 (coding exon 2) of the ARCN1 gene. This alteration results from a A to G substitution at nucleotide position 85, causing the isoleucine (I) at amino acid position 29 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T;T;.;T
Eigen	Benign	-0.046
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	.;.;.;L
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.66	.;N;N;N
REVEL	Benign	0.075
Sift	Benign	0.11	.;T;T;T
Sift4G	Benign	0.29	T;T;T;T
Polyphen		0.017, 0.046, 0.067	.;B;B;B
Vest4		0.16
MutPred		0.54		.;Loss of catalytic residue at I70 (P = 0.0155);.;.;
MVP		0.42
MPC		0.60
ClinPred		0.64	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.13
gMVP		0.38

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-118452042;