6-35737299-C-T

Variant names:

• chr6-35737299-C-T
• rs386352286
• ENST00000288065.6:c.191C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_145028.5(ARMC12):​c.191C>T​(p.Ala64Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ARMC12 NM_145028.5 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 0.634
• Publications: 1 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• 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=0.1786007).

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+28C>T		intron	N/A	NP_001273503.1	Q5T9G4-1
	ARMC12	NM_145028.5		c.191C>T	p.Ala64Val	missense	Exon 1 of 6	NP_659465.2
	ARMC12	NM_001286576.2		c.163+28C>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.191C>T	p.Ala64Val	missense	Exon 1 of 6	ENSP00000288065.2	Q5T9G4-2
	ARMC12	ENST00000373866.4	TSL:3 MANE Select	c.163+28C>T		intron	N/A	ENSP00000362973.3	Q5T9G4-1
	ARMC12	ENST00000373869.7	TSL:2	c.163+28C>T		intron	N/A	ENSP00000362976.3	Q5T9G4-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: no assertion criteria provided

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Uncertain	1.0
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.63
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.068
Sift	Benign	0.083	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.87	P
Vest4		0.24
MutPred		0.17		Loss of glycosylation at P60 (P = 0.1786)
MVP		0.55
MPC		0.22
ClinPred		0.96	D
GERP RS		4.9
PromoterAI		-0.0067	Neutral
gMVP		0.13
Mutation Taster		=78/22	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: rs386352286; hg19: chr6-35705076;