NM_001352754.2:c.52-11_52-8delATTT

Variant names:

• chr2-231208109-ATTAT-A
• rs1559286587
• NM_001352754.2:c.52-11_52-8delATTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP6_Moderate

The NM_001352754.2(ARMC9):​c.52-11_52-8delATTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000316 in 950,758 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: ARMC9 NM_001352754.2 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.08
• 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: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 2-231208109-ATTAT-A is Benign according to our data. Variant chr2-231208109-ATTAT-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2007025.Status of the report is criteria_provided_single_submitter, 1 stars.

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.52-11_52-8delATTT		splice_region intron	N/A	NP_001339683.2	Q7Z3E5-1
	ARMC9	NM_001271466.4		c.52-11_52-8delATTT		splice_region intron	N/A	NP_001258395.2	Q7Z3E5-1
	ARMC9	NM_001291656.2		c.52-11_52-8delATTT		splice_region intron	N/A	NP_001278585.2	A0A2Q3DP09

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC9	ENST00000611582.5	TSL:5 MANE Select	c.52-17_52-14delTTAT		intron	N/A	ENSP00000484804.1	Q7Z3E5-1
	ARMC9	ENST00000349938.8	TSL:1	c.52-17_52-14delTTAT		intron	N/A	ENSP00000258417.5	A0A2Q3DP09
	ARMC9	ENST00000958134.1		c.52-17_52-14delTTAT		intron	N/A	ENSP00000628193.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000626 AC: 1 AN: 159648 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000316 AC: 3 AN: 950758 Hom.: 0 AF XY: 0.00000409 AC XY: 2 AN XY: 488648

African (AFR) AF: 0.00 AC: 0 AN: 20874

American (AMR) AF: 0.00 AC: 0 AN: 29560

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21538

East Asian (EAS) AF: 0.00 AC: 0 AN: 33884

South Asian (SAS) AF: 0.0000449 AC: 3 AN: 66756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48900

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4428

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 681840

Other (OTH) AF: 0.00 AC: 0 AN: 42978

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.21		Position offset: 18

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1559286587; hg19: chr2-232072822;