rs2817041

Variant names:

• chr6-35738115-T-C
• rs2817041
• NM_001286574.2:c.252T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001286574.2(ARMC12):​c.252T>C​(p.Tyr84Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 1,613,732 control chromosomes in the GnomAD database, including 513,953 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 0.79 (48053 hom., cov: 31)
  • Exomes 𝑓: 0.80 (465900 hom.)
• Consequence: ARMC12 NM_001286574.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.487
• Publications: 18 publications found

Genes affected

ARMC12 (HGNC:21099): (armadillo repeat containing 12) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP7: Synonymous conserved (PhyloP=0.487 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286574.2. 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
	ARMC12	NM_001286574.2	MANE Select	c.252T>C	p.Tyr84Tyr	synonymous	Exon 2 of 6	NP_001273503.1	Q5T9G4-1
	ARMC12	NM_145028.5		c.333T>C	p.Tyr111Tyr	synonymous	Exon 2 of 6	NP_659465.2
	ARMC12	NM_001286576.2		c.252T>C	p.Tyr84Tyr	synonymous	Exon 2 of 6	NP_001273505.1	Q5T9G4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC12	ENST00000373866.4	TSL:3 MANE Select	c.252T>C	p.Tyr84Tyr	synonymous	Exon 2 of 6	ENSP00000362973.3	Q5T9G4-1
	ARMC12	ENST00000288065.6	TSL:1	c.333T>C	p.Tyr111Tyr	synonymous	Exon 2 of 6	ENSP00000288065.2	Q5T9G4-2
	ARMC12	ENST00000373869.7	TSL:2	c.252T>C	p.Tyr84Tyr	synonymous	Exon 2 of 6	ENSP00000362976.3	Q5T9G4-3

Frequencies

GnomAD3 genomes AF: 0.794 AC: 120557 AN: 151912 Hom.: 47999 Cov.: 31

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.958

Gnomad AMR AF: 0.809

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.809

GnomAD2 exomes AF: 0.794 AC: 199495 AN: 251280 AF XY: 0.790

Gnomad AFR exome AF: 0.787

Gnomad AMR exome AF: 0.847

Gnomad ASJ exome AF: 0.796

Gnomad EAS exome AF: 0.599

Gnomad FIN exome AF: 0.842

Gnomad NFE exome AF: 0.810

Gnomad OTH exome AF: 0.800

GnomAD4 exome AF: 0.797 AC: 1165229 AN: 1461702 Hom.: 465900 Cov.: 72 AF XY: 0.796 AC XY: 578832 AN XY: 727160

African (AFR) AF: 0.786 AC: 26307 AN: 33480

American (AMR) AF: 0.845 AC: 37812 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.802 AC: 20951 AN: 26136

East Asian (EAS) AF: 0.600 AC: 23816 AN: 39700

South Asian (SAS) AF: 0.758 AC: 65378 AN: 86258

European-Finnish (FIN) AF: 0.838 AC: 44626 AN: 53260

Middle Eastern (MID) AF: 0.784 AC: 4517 AN: 5764

European-Non Finnish (NFE) AF: 0.804 AC: 893721 AN: 1111986

Other (OTH) AF: 0.796 AC: 48101 AN: 60394

GnomAD4 genome AF: 0.794 AC: 120671 AN: 152030 Hom.: 48053 Cov.: 31 AF XY: 0.792 AC XY: 58811 AN XY: 74298

African (AFR) AF: 0.783 AC: 32466 AN: 41456

American (AMR) AF: 0.809 AC: 12364 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2758 AN: 3466

East Asian (EAS) AF: 0.581 AC: 2989 AN: 5148

South Asian (SAS) AF: 0.747 AC: 3593 AN: 4812

European-Finnish (FIN) AF: 0.838 AC: 8858 AN: 10572

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54825 AN: 67996

Other (OTH) AF: 0.812 AC: 1705 AN: 2100

Alfa AF: 0.795 Hom.: 29994

Bravo AF: 0.796

Asia WGS AF: 0.754 AC: 2622 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.9
DANN	Benign	0.82
PhyloP100		0.49
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2817041; hg19: chr6-35705892; COSMIC: COSV55361145; COSMIC: COSV55361145;