NM_001352754.2:c.141C>T

Variant names:

• chr2-231208216-C-T
• rs35643982
• NM_001352754.2:c.141C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001352754.2(ARMC9):​c.141C>T​(p.Gly47Gly) 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:3
• Conservation: PhyloP100: -0.273
• 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 -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 VariationId 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.

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.141C>T	p.Gly47Gly	synonymous	Exon 3 of 25	NP_001339683.2	Q7Z3E5-1
	ARMC9	NM_001271466.4		c.141C>T	p.Gly47Gly	synonymous	Exon 3 of 25	NP_001258395.2	Q7Z3E5-1
	ARMC9	NM_001291656.2		c.141C>T	p.Gly47Gly	synonymous	Exon 3 of 21	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.141C>T	p.Gly47Gly	synonymous	Exon 3 of 25	ENSP00000484804.1	Q7Z3E5-1
	ARMC9	ENST00000349938.8	TSL:1	c.141C>T	p.Gly47Gly	synonymous	Exon 3 of 21	ENSP00000258417.5	A0A2Q3DP09
	ARMC9	ENST00000958134.1		c.141C>T	p.Gly47Gly	synonymous	Exon 3 of 26	ENSP00000628193.1

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

GnomAD2 exomes AF: 0.0483 AC: 11993 AN: 248508 AF XY: 0.0490

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 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

African (AFR) AF: 0.00999 AC: 333 AN: 33320

American (AMR) AF: 0.0282 AC: 1236 AN: 43884

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 886 AN: 26040

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39606

South Asian (SAS) AF: 0.0221 AC: 1888 AN: 85256

European-Finnish (FIN) AF: 0.0783 AC: 4174 AN: 53338

Middle Eastern (MID) AF: 0.0104 AC: 60 AN: 5760

European-Non Finnish (NFE) AF: 0.0744 AC: 82483 AN: 1108992

Other (OTH) AF: 0.0555 AC: 3340 AN: 60218

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

African (AFR) AF: 0.0124 AC: 514 AN: 41550

American (AMR) AF: 0.0347 AC: 530 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 116 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0195 AC: 94 AN: 4824

European-Finnish (FIN) AF: 0.0680 AC: 720 AN: 10594

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0732 AC: 4979 AN: 68024

Other (OTH) AF: 0.0450 AC: 95 AN: 2112

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	8.2
DANN	Benign	0.58
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35643982; hg19: chr2-232072929;