rs202136403

Variant names:

• chr6-35738057-G-A
• rs202136403
• NM_001286574.2:c.194G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-35738057-G-A
• chr6-35738057-G-C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP2 BP4_Strong

The NM_001286574.2(ARMC12):​c.194G>A​(p.Arg65Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,613,922 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: ARMC12 NM_001286574.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.95
• Publications: 2 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: Likely_benign. The variant received -3 ACMG points.

• PP2: Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 3 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.27213 (below the threshold of 3.09). Trascript score misZ: 1.0694 (below the threshold of 3.09).
• BP4: Computational evidence support a benign effect (MetaRNN=0.06647545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMC12	NM_001286574.2	c.194G>A	p.Arg65Gln	missense_variant	Exon 2 of 6	ENST00000373866.4	NP_001273503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMC12	ENST00000373866.4	c.194G>A	p.Arg65Gln	missense_variant	Exon 2 of 6	3	NM_001286574.2	ENSP00000362973.3

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 43 AN: 152192 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000175 AC: 44 AN: 251134 AF XY: 0.000206

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000967

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000159 AC: 232 AN: 1461612 Hom.: 1 Cov.: 30 AF XY: 0.000176 AC XY: 128 AN XY: 727104

African (AFR) AF: 0.000179 AC: 6 AN: 33480

American (AMR) AF: 0.000380 AC: 17 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000707 AC: 61 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53156

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.000127 AC: 141 AN: 1112010

Other (OTH) AF: 0.0000994 AC: 6 AN: 60388

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152310 Hom.: 0 Cov.: 33 AF XY: 0.000416 AC XY: 31 AN XY: 74472

African (AFR) AF: 0.0000722 AC: 3 AN: 41572

American (AMR) AF: 0.00203 AC: 31 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.000238

ExAC AF: 0.000140 AC: 17

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 07, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.275G>A (p.R92Q) alteration is located in exon 2 (coding exon 2) of the ARMC12 gene. This alteration results from a G to A substitution at nucleotide position 275, causing the arginine (R) at amino acid position 92 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	.;.;T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.066	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.;L
PhyloP100		2.0
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.27	N;N;N
REVEL	Benign	0.14
Sift	Benign	0.11	T;T;T
Sift4G	Benign	0.21	T;T;T
Polyphen		0.88	P;P;.
Vest4		0.44
MVP		0.72
MPC		0.31
ClinPred		0.037	T
GERP RS		4.5
Varity_R		0.075
gMVP		0.15
Mutation Taster		=97/3	polymorphism

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: rs202136403; hg19: chr6-35705834; COSMIC: COSV104601614; COSMIC: COSV104601614;