2-231206193-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001352754.2(ARMC9):c.-41-5T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0037 in 1,558,698 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (103 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (70 hom.)
• Consequence: ARMC9 NM_001352754.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0002805
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.49

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 2-231206193-T-C is Benign according to our data. Variant chr2-231206193-T-C is described in ClinVar as [Benign]. Clinvar id is 1226717.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMC9	NM_001352754.2	c.-41-5T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000611582.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMC9	ENST00000611582.5	c.-41-5T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5	NM_001352754.2	P1

Frequencies

GnomAD3 genomes AF: 0.0197 AC: 2992 AN: 152196 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00530

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0120

GnomAD3 exomes AF: 0.00526 AC: 1313 AN: 249504 Hom.: 39 AF XY: 0.00384 AC XY: 518 AN XY: 135044

Gnomad AFR exome AF: 0.0729

Gnomad AMR exome AF: 0.00344

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000662

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000115

Gnomad OTH exome AF: 0.00214

GnomAD4 exome AF: 0.00197 AC: 2765 AN: 1406384 Hom.: 70 Cov.: 24 AF XY: 0.00168 AC XY: 1179 AN XY: 703044

Gnomad4 AFR exome AF: 0.0700

Gnomad4 AMR exome AF: 0.00366

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000106

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000791

Gnomad4 OTH exome AF: 0.00427

GnomAD4 genome AF: 0.0197 AC: 3000 AN: 152314 Hom.: 103 Cov.: 32 AF XY: 0.0189 AC XY: 1405 AN XY: 74474

Gnomad4 AFR AF: 0.0694

Gnomad4 AMR AF: 0.00529

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00775 Hom.: 9

Bravo AF: 0.0221

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	12
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00028
dbscSNV1_RF	Benign	0.0060
SpliceAI score (max)		0.17		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: rs74651652; hg19: chr2-232070906;