rs886040860

Positions:

• chr11-118583990-CA-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_001655.5(ARCN1):​c.633delA​(p.Val212fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARCN1 NM_001655.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.00

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 Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-118583990-CA-C is Pathogenic according to our data. Variant chr11-118583990-CA-C is described in ClinVar as [Pathogenic]. Clinvar id is 267210.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARCN1	NM_001655.5	c.633delA	p.Val212fs	frameshift_variant	4/10	ENST00000264028.5	NP_001646.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARCN1	ENST00000264028.5	c.633delA	p.Val212fs	frameshift_variant	4/10	1	NM_001655.5	ENSP00000264028.4
ARCN1	ENST00000359415.8	c.756delA	p.Val253fs	frameshift_variant	5/11	1		ENSP00000352385.4
ARCN1	ENST00000392859.7	c.369delA	p.Val124fs	frameshift_variant	3/9	2		ENSP00000376599.3
ARCN1	ENST00000534182.2	c.159+2593delA		intron_variant		5		ENSP00000431676.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Sep 06, 2022

- -

Computational scores

Source: dbNSFP v4.3

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: rs886040860; hg19: chr11-118454705;