rs1553618510

Variant names:

• chr2-231296244-AGAT-A
• rs1553618510
• NM_001352754.2:c.1770_1772delTGA

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP3

The NM_001352754.2(ARMC9):​c.1770_1772delTGA​(p.Asp590del) variant causes a disruptive inframe deletion, splice region change. The variant allele was found at a frequency of 0.00000479 in 1,460,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: ARMC9 NM_001352754.2 disruptive_inframe_deletion, splice_region
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 4.60
• Publications: 0 publications found

Genes affected

ARMC9 (HGNC:20730): (armadillo repeat containing 9) Predicted to be involved in cilium assembly and positive regulation of smoothened signaling pathway. Located in centriole and ciliary basal body. Implicated in Joubert syndrome 30. [provided by Alliance of Genome Resources, Apr 2022]

ARMC9 Gene-Disease associations (from GenCC):

• Joubert syndrome 30

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP3: Nonframeshift variant in repetitive region in NM_001352754.2

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352754.2. 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
	ARMC9	NM_001352754.2	MANE Select	c.1770_1772delTGA	p.Asp590del	disruptive_inframe_deletion splice_region	Exon 19 of 25	NP_001339683.2
	ARMC9	NM_001271466.4		c.1770_1772delTGA	p.Asp590del	disruptive_inframe_deletion splice_region	Exon 19 of 25	NP_001258395.2
	ARMC9	NM_001291656.2		c.1770_1772delTGA	p.Asp590del	disruptive_inframe_deletion splice_region	Exon 19 of 21	NP_001278585.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC9	ENST00000611582.5	TSL:5 MANE Select	c.1770_1772delTGA	p.Asp590del	disruptive_inframe_deletion splice_region	Exon 19 of 25	ENSP00000484804.1
	ARMC9	ENST00000349938.8	TSL:1	c.1770_1772delTGA	p.Asp590del	disruptive_inframe_deletion splice_region	Exon 19 of 21	ENSP00000258417.5
	ARMC9	ENST00000958134.1		c.1770_1772delTGA	p.Asp590del	disruptive_inframe_deletion splice_region	Exon 19 of 26	ENSP00000628193.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460886 Hom.: 0 AF XY: 0.00000550 AC XY: 4 AN XY: 726756

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86074

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111442

Other (OTH) AF: 0.0000166 AC: 1 AN: 60350

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	ARMC9-related Joubert syndrome (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.6

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: rs1553618510; hg19: chr2-232160957;