chr2-231322443-C-T

Variant names:

• chr2-231322443-C-T
• rs6753112
• NM_001352754.2:c.1774-9350C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352754.2(ARMC9):​c.1774-9350C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 152,184 control chromosomes in the GnomAD database, including 25,152 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.54 (25152 hom., cov: 34)
• Consequence: ARMC9 NM_001352754.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.535
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

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.1774-9350C>T		intron	N/A	NP_001339683.2	Q7Z3E5-1
	ARMC9	NM_001271466.4		c.1774-9350C>T		intron	N/A	NP_001258395.2	Q7Z3E5-1
	ARMC9	NM_001291656.2		c.1774-9350C>T		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.1774-9350C>T		intron	N/A	ENSP00000484804.1	Q7Z3E5-1
	ARMC9	ENST00000349938.8	TSL:1	c.1774-9350C>T		intron	N/A	ENSP00000258417.5	A0A2Q3DP09
	ARMC9	ENST00000958134.1		c.1774-9350C>T		intron	N/A	ENSP00000628193.1

Frequencies

GnomAD3 genomes AF: 0.536 AC: 81456 AN: 152066 Hom.: 25100 Cov.: 34

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.504

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.536 AC: 81564 AN: 152184 Hom.: 25152 Cov.: 34 AF XY: 0.534 AC XY: 39713 AN XY: 74408

African (AFR) AF: 0.863 AC: 35856 AN: 41552

American (AMR) AF: 0.413 AC: 6321 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1670 AN: 3472

East Asian (EAS) AF: 0.620 AC: 3213 AN: 5182

South Asian (SAS) AF: 0.453 AC: 2183 AN: 4818

European-Finnish (FIN) AF: 0.458 AC: 4834 AN: 10562

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.381 AC: 25911 AN: 67982

Other (OTH) AF: 0.503 AC: 1064 AN: 2116

Alfa AF: 0.421 Hom.: 24964

Bravo AF: 0.547

Asia WGS AF: 0.571 AC: 1986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6753112; hg19: chr2-232187155;