2-231208216-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001352754.2(ARMC9):c.141C>T(p.Gly47=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 1,608,666 control chromosomes in the GnomAD database, including 3,725 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (249 hom., cov: 33)
  • Exomes 𝑓: 0.065 (3476 hom.)
• Consequence: ARMC9 NM_001352754.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.273

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 2-231208216-C-T is Benign according to our data. Variant chr2-231208216-C-T is described in ClinVar as [Benign]. Clinvar id is 1170309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.273 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMC9	NM_001352754.2	c.141C>T	p.Gly47=	synonymous_variant	3/25	ENST00000611582.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMC9	ENST00000611582.5	c.141C>T	p.Gly47=	synonymous_variant	3/25	5	NM_001352754.2	P1

Frequencies

GnomAD3 genomes AF: 0.0469 AC: 7137 AN: 152134 Hom.: 249 Cov.: 33

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0879

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0680

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0732

Gnomad OTH AF: 0.0455

GnomAD3 exomes AF: 0.0483 AC: 11993 AN: 248508 Hom.: 411 AF XY: 0.0490 AC XY: 6582 AN XY: 134276

Gnomad AFR exome AF: 0.0112

Gnomad AMR exome AF: 0.0266

Gnomad ASJ exome AF: 0.0357

Gnomad EAS exome AF: 0.000164

Gnomad SAS exome AF: 0.0216

Gnomad FIN exome AF: 0.0747

Gnomad NFE exome AF: 0.0709

Gnomad OTH exome AF: 0.0470

GnomAD4 exome AF: 0.0648 AC: 94406 AN: 1456414 Hom.: 3476 Cov.: 31 AF XY: 0.0638 AC XY: 46227 AN XY: 724518

Gnomad4 AFR exome AF: 0.00999

Gnomad4 AMR exome AF: 0.0282

Gnomad4 ASJ exome AF: 0.0340

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.0221

Gnomad4 FIN exome AF: 0.0783

Gnomad4 NFE exome AF: 0.0744

Gnomad4 OTH exome AF: 0.0555

GnomAD4 genome AF: 0.0469 AC: 7134 AN: 152252 Hom.: 249 Cov.: 33 AF XY: 0.0454 AC XY: 3377 AN XY: 74456

Gnomad4 AFR AF: 0.0124

Gnomad4 AMR AF: 0.0347

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0195

Gnomad4 FIN AF: 0.0680

Gnomad4 NFE AF: 0.0732

Gnomad4 OTH AF: 0.0450

Alfa AF: 0.0624 Hom.: 168

Bravo AF: 0.0444

Asia WGS AF: 0.00895 AC: 31 AN: 3478

EpiCase AF: 0.0652

EpiControl AF: 0.0652

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	8.2
Dann	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs35643982; hg19: chr2-232072929;