Variant 6-35738048-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001286574.2(ARMC12):c.185G>A(p.Arg62Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,440 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

ARMC12
NM_001286574.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

Variant links:

Genes affected

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

ARMC12 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1427297).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMC12	NM_001286574.2 linkuse as main transcript	c.185G>A	p.Arg62Gln	missense_variant	2/6	ENST00000373866.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMC12	ENST00000373866.4 linkuse as main transcript	c.185G>A	p.Arg62Gln	missense_variant	2/6	3	NM_001286574.2	A1	Q5T9G4-1
ARMC12	ENST00000288065.6 linkuse as main transcript	c.266G>A	p.Arg89Gln	missense_variant	2/6	1		P3	Q5T9G4-2
ARMC12	ENST00000373869.7 linkuse as main transcript	c.185G>A	p.Arg62Gln	missense_variant	2/6	2			Q5T9G4-3
ARMC12	ENST00000471400.1 linkuse as main transcript	c.*45G>A		3_prime_UTR_variant, NMD_transcript_variant	2/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250928

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461440

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2023

The c.266G>A (p.R89Q) 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 266, causing the arginine (R) at amino acid position 89 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

0.088

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.023

.;.;T

Eigen

Benign

0.035

Eigen_PC

Benign

0.14

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.0066

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

M;.;M

MutationTaster

Benign

0.52

D;D;D

PrimateAI

Benign

0.38

PROVEAN

Benign

0.15

N;N;N

REVEL

Benign

0.052

Sift

Benign

0.30

T;T;T

Sift4G

Uncertain

0.021

D;D;D

Polyphen

0.37

B;D;.

Vest4

0.27

MutPred

0.42

.;Loss of MoRF binding (P = 0.0355);.;

MVP

0.58

MPC

0.15

ClinPred

0.35

GERP RS

4.7

Varity_R

0.089

gMVP

0.27

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over