Variant X-101616352-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The ENST00000361910.9(ARMCX6):c.269G>A(p.Gly90Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000207 in 1,209,427 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000021 ( 0 hom. 6 hem. )

Consequence

ARMCX6
ENST00000361910.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.03

Variant links:

Genes affected

ARMCX6 (HGNC:26094): (armadillo repeat containing X-linked 6) Predicted to be located in mitochondrial outer membrane. Predicted to be integral component of membrane. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ARMCX6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.35228586).

BS2

High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMCX6	NM_019007.4 linkuse as main transcript	c.269G>A	p.Gly90Glu	missense_variant	3/3	ENST00000361910.9	NP_061880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMCX6	ENST00000361910.9 linkuse as main transcript	c.269G>A	p.Gly90Glu	missense_variant	3/3	1	NM_019007.4	ENSP00000354708	P1

Frequencies

GnomAD3 genomes

AF:

0.0000180

AC:

AN:

111165

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33367

show subpopulations

Gnomad AFR

AF:

0.0000656

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000209

AC:

AN:

1098262

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

363616

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000261

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000180

AC:

AN:

111165

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33367

show subpopulations

Gnomad4 AFR

AF:

0.0000656

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Jun 29, 2022

The c.269G>A (p.G90E) alteration is located in exon 4 (coding exon 1) of the ARMCX6 gene. This alteration results from a G to A substitution at nucleotide position 269, causing the glycine (G) at amino acid position 90 to be replaced by a glutamic acid (E). 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

0.57

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0075

T;T;T

FATHMM_MKL

Benign

0.69

LIST_S2

Benign

0.57

.;.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.35

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.0

L;L;L

MutationTaster

Benign

0.64

D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.19

Sift

Benign

0.092

T;T;T

Sift4G

Benign

0.15

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.35

MutPred

0.40

Gain of solvent accessibility (P = 0.0026);Gain of solvent accessibility (P = 0.0026);Gain of solvent accessibility (P = 0.0026);

MVP

0.94

MPC

0.88

ClinPred

0.82

GERP RS

3.6

Varity_R

0.16

gMVP

0.14

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