Variant 6-35747274-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001286574.2(ARMC12):c.458A>T(p.Lys153Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00114 in 1,612,032 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 1 hom. )

Consequence

ARMC12
NM_001286574.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92

Variant links:

Genes affected

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

ARMC12 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41339543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARMC12	NM_001286574.2 linkuse as main transcript	c.458A>T	p.Lys153Ile	missense_variant	4/6	ENST00000373866.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARMC12	ENST00000373866.4 linkuse as main transcript	c.458A>T	p.Lys153Ile	missense_variant	4/6	3	NM_001286574.2	A1	Q5T9G4-1
ARMC12	ENST00000288065.6 linkuse as main transcript	c.539A>T	p.Lys180Ile	missense_variant	4/6	1		P3	Q5T9G4-2
ARMC12	ENST00000373869.7 linkuse as main transcript	c.458A>T	p.Lys153Ile	missense_variant	4/6	2			Q5T9G4-3

Frequencies

GnomAD3 genomes

AF:

0.000809

AC:

123

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00166

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000653

AC:

164

AN:

250964

Hom.:

AF XY:

0.000642

AC XY:

AN XY:

135602

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000324

Gnomad NFE exome

AF:

0.00128

Gnomad OTH exome

AF:

0.000817

GnomAD4 exome

AF:

0.00117

AC:

1712

AN:

1459934

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

813

AN XY:

726244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00148

Gnomad4 OTH exome

AF:

0.000730

GnomAD4 genome

AF:

0.000809

AC:

123

AN:

152098

Hom.:

Cov.:

AF XY:

0.000659

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00166

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.000778

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000659

AC:

EpiCase

AF:

0.00142

EpiControl

AF:

0.000830

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

Oct 29, 2021

The c.539A>T (p.K180I) alteration is located in exon 4 (coding exon 4) of the ARMC12 gene. This alteration results from a A to T substitution at nucleotide position 539, causing the lysine (K) at amino acid position 180 to be replaced by an isoleucine (I). 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

Pathogenic

0.81

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

.;.;T

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.055

MetaRNN

Benign

0.41

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.1

M;.;M

MutationTaster

Benign

0.79

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.0040

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.97

D;D;.

Vest4

0.71

MVP

0.59

MPC

0.71

ClinPred

0.12

GERP RS

4.4

Varity_R

0.34

gMVP

0.30

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

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