6-35737281-C-T

Variant names:

• chr6-35737281-C-T
• rs150052894
• ENST00000288065.6:c.173C>T

Variant summary

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

The NM_145028.5(ARMC12):​c.173C>T​(p.Pro58Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,614,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: ARMC12 NM_145028.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.509
• Publications: 0 publications found

Genes affected

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

ENSG00000232909 (HGNC:):

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: 1.0468 (below the threshold of 3.09).
• BP4: Computational evidence support a benign effect (MetaRNN=0.020891339).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145028.5. 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.163+10C>T		intron	N/A	NP_001273503.1	Q5T9G4-1
	ARMC12	NM_145028.5		c.173C>T	p.Pro58Leu	missense	Exon 1 of 6	NP_659465.2
	ARMC12	NM_001286576.2		c.163+10C>T		intron	N/A	NP_001273505.1	Q5T9G4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMC12	ENST00000288065.6	TSL:1	c.173C>T	p.Pro58Leu	missense	Exon 1 of 6	ENSP00000288065.2	Q5T9G4-2
	ARMC12	ENST00000373866.4	TSL:3 MANE Select	c.163+10C>T		intron	N/A	ENSP00000362973.3	Q5T9G4-1
	ARMC12	ENST00000373869.7	TSL:2	c.163+10C>T		intron	N/A	ENSP00000362976.3	Q5T9G4-3

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152246 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000955 AC: 24 AN: 251336 AF XY: 0.0000883

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000520

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000280 AC: 41 AN: 1461874 Hom.: 0 Cov.: 32 AF XY: 0.0000289 AC XY: 21 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000492 AC: 22 AN: 44724

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

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.0000117 AC: 13 AN: 1112004

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.0000525 AC: 8 AN: 152364 Hom.: 0 Cov.: 33 AF XY: 0.0000537 AC XY: 4 AN XY: 74502

African (AFR) AF: 0.00 AC: 0 AN: 41590

American (AMR) AF: 0.000131 AC: 2 AN: 15306

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68034

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

Alfa AF: 0.0000772 Hom.: 0

Bravo AF: 0.0000982

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	19
DANN	Uncertain	0.98
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.53	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.51
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.024
Sift	Uncertain	0.026	D
Sift4G	Benign	0.16	T
Polyphen		0.0	B
Vest4		0.28
MVP		0.19
MPC		0.11
ClinPred		0.060	T
GERP RS		2.0
PromoterAI		0.020	Neutral
gMVP		0.17
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs150052894; hg19: chr6-35705058;