Genetic Variant NM_016608.2:c.493G>A (chrX-101553423-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_016608.2(ARMCX1):c.493G>A(p.Ala165Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000335 in 1,195,148 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

ARMCX1
NM_016608.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.43

Publications

1 publications found

Variant links:

Genes affected

ARMCX1 (HGNC:18073): (armadillo repeat containing X-linked 1) This gene encodes a member of the ALEX family of proteins and may play a role in tumor suppression. The encoded protein contains a potential N-terminal transmembrane domain and two Armadillo (arm) repeats. Other proteins containing the arm repeat are involved in development, maintenance of tissue integrity, and tumorigenesis. This gene is closely localized with other family members, including ALEX2 and ALEX3, on the X chromosome. [provided by RefSeq, Jul 2008]

ARMCX1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018884093).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016608.2. 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
	ARMCX1	NM_016608.2	MANE Select	c.493G>A	p.Ala165Thr	missense	Exon 4 of 4	NP_057692.1	Q9P291

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARMCX1	ENST00000372829.8	TSL:1 MANE Select	c.493G>A	p.Ala165Thr	missense	Exon 4 of 4	ENSP00000361917.3	Q9P291
ARMCX1	ENST00000898854.1		c.493G>A	p.Ala165Thr	missense	Exon 4 of 4	ENSP00000568913.1
ARMCX1	ENST00000898855.1		c.493G>A	p.Ala165Thr	missense	Exon 3 of 3	ENSP00000568914.1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111526

Hom.:

Cov.:

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:

0.000566

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

GnomAD2 exomes

AF:

0.00000605

AC:

AN:

165359

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000741

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000185

AC:

AN:

1083570

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

352992

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26008

American (AMR)

AF:

0.00

AC:

AN:

33690

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18249

East Asian (EAS)

AF:

0.0000664

AC:

AN:

30129

South Asian (SAS)

AF:

0.00

AC:

AN:

51040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40003

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4044

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

834967

Other (OTH)

AF:

0.00

AC:

AN:

45440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111578

Hom.:

Cov.:

AF XY:

0.0000296

AC XY:

AN XY:

33766

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30724

American (AMR)

AF:

0.00

AC:

AN:

10588

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.000568

AC:

AN:

3522

South Asian (SAS)

AF:

0.00

AC:

AN:

2605

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6034

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53030

Other (OTH)

AF:

0.00

AC:

AN:

1527

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.37

(source)

DANN

Benign

0.30

DEOGEN2

Benign

0.021

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.44

M_CAP

Benign

0.0033

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

-1.4

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.59

REVEL

Benign

0.0090

Sift

Benign

0.21

Sift4G

Benign

0.29

Polyphen

0.0

Vest4

0.062

MVP

0.48

MPC

0.59

ClinPred

0.0072

GERP RS

-3.3

Varity_R

0.061

gMVP

0.37

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over