Variant chrX-101616262-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000361910.9(ARMCX6):c.359A>G(p.Asn120Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000678 in 1,209,134 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 34 hemizygotes in GnomAD. 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 0.000036 ( 0 hom., 2 hem., cov: 21)

Exomes 𝑓: 0.000071 ( 0 hom. 32 hem. )

Consequence

ARMCX6
ENST00000361910.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.230

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07650757).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMCX6	NM_019007.4 linkuse as main transcript	c.359A>G	p.Asn120Ser	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.359A>G	p.Asn120Ser	missense_variant	3/3	1	NM_019007.4	ENSP00000354708	P1

Frequencies

GnomAD3 genomes

AF:

0.0000361

AC:

AN:

110869

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

33073

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000756

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183437

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

67881

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000244

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000710

AC:

AN:

1098265

Hom.:

Cov.:

AF XY:

0.0000880

AC XY:

AN XY:

363619

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000926

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000361

AC:

AN:

110869

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

33073

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000756

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000529

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

Sep 16, 2021

The c.359A>G (p.N120S) alteration is located in exon 4 (coding exon 1) of the ARMCX6 gene. This alteration results from a A to G substitution at nucleotide position 359, causing the asparagine (N) at amino acid position 120 to be replaced by a serine (S). 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

0.083

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.50

DANN

Benign

0.55

DEOGEN2

Benign

0.0060

T;T;T

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.43

.;.;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.077

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.37

N;N;N

REVEL

Benign

0.051

Sift

Benign

0.17

T;T;T

Sift4G

Benign

0.72

T;T;T

Polyphen

0.0040

B;B;B

Vest4

0.076

MutPred

0.52

Gain of catalytic residue at N120 (P = 0.003);Gain of catalytic residue at N120 (P = 0.003);Gain of catalytic residue at N120 (P = 0.003);

MVP

0.63

MPC

0.16

ClinPred

0.059

GERP RS

0.10

Varity_R

0.029

gMVP

0.053

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