2-231327593-C-T

Variant names:

• chr2-231327593-C-T
• rs1669070
• NM_001352754.2:c.1774-4200C>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.1774-4200C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.356 in 152,010 control chromosomes in the GnomAD database, including 9,972 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 0.36 (9972 hom., cov: 32)
• Consequence: ARMC9 NM_001352754.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC9	NM_001352754.2	c.1774-4200C>T		intron_variant	Intron 19 of 24	ENST00000611582.5	NP_001339683.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC9	ENST00000611582.5	c.1774-4200C>T		intron_variant	Intron 19 of 24	5	NM_001352754.2	ENSP00000484804.1

Frequencies

GnomAD3 genomes AF: 0.356 AC: 54010 AN: 151892 Hom.: 9964 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.356 AC: 54053 AN: 152010 Hom.: 9972 Cov.: 32 AF XY: 0.361 AC XY: 26824 AN XY: 74310

African (AFR) AF: 0.275 AC: 11377 AN: 41446

American (AMR) AF: 0.343 AC: 5246 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1634 AN: 3470

East Asian (EAS) AF: 0.321 AC: 1663 AN: 5176

South Asian (SAS) AF: 0.419 AC: 2019 AN: 4814

European-Finnish (FIN) AF: 0.487 AC: 5131 AN: 10538

Middle Eastern (MID) AF: 0.421 AC: 123 AN: 292

European-Non Finnish (NFE) AF: 0.379 AC: 25756 AN: 67976

Other (OTH) AF: 0.375 AC: 792 AN: 2112

Alfa AF: 0.366 Hom.: 26734

Bravo AF: 0.345

Asia WGS AF: 0.357 AC: 1239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.40
DANN	Benign	0.33
PhyloP100		-1.4
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: rs1669070; hg19: chr2-232192305;