dbSNP rs782411889: ARMCX1:p.Asp32Glu (chrX-101553026-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_016608.2(ARMCX1):c.96C>A(p.Asp32Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000802 in 1,209,545 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 31 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000063 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000082 ( 0 hom. 30 hem. )

Consequence

ARMCX1
NM_016608.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.316

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14195108).

BS2

High Hemizygotes in GnomAdExome4 at 30 gene

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.96C>A	p.Asp32Glu	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.96C>A	p.Asp32Glu	missense	Exon 4 of 4	ENSP00000361917.3	Q9P291
ARMCX1	ENST00000898854.1		c.96C>A	p.Asp32Glu	missense	Exon 4 of 4	ENSP00000568913.1
ARMCX1	ENST00000898855.1		c.96C>A	p.Asp32Glu	missense	Exon 3 of 3	ENSP00000568914.1

Frequencies

GnomAD3 genomes

AF:

0.0000628

AC:

AN:

111379

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000327

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:

0.000113

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000602

AC:

AN:

182869

AF XY:

0.0000593

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000146

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000859

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000820

AC:

AN:

1098166

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

363522

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26403

American (AMR)

AF:

0.000142

AC:

AN:

35200

Ashkenazi Jewish (ASJ)

AF:

0.0000516

AC:

AN:

19384

East Asian (EAS)

AF:

0.00

AC:

AN:

30203

South Asian (SAS)

AF:

0.00

AC:

AN:

54132

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40513

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.0000914

AC:

AN:

842099

Other (OTH)

AF:

0.000152

AC:

AN:

46095

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.0000628

AC:

AN:

111379

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

33615

show subpopulations

African (AFR)

AF:

0.0000327

AC:

AN:

30574

American (AMR)

AF:

0.00

AC:

AN:

10499

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2638

East Asian (EAS)

AF:

0.00

AC:

AN:

3528

South Asian (SAS)

AF:

0.00

AC:

AN:

2651

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6005

Middle Eastern (MID)

AF:

0.00

AC:

AN:

235

European-Non Finnish (NFE)

AF:

0.000113

AC:

AN:

53078

Other (OTH)

AF:

0.00

AC:

AN:

1490

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

Genome Het

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:

0.000142

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

0.10

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.74

CADD

Benign

6.1

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.032

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.45

M_CAP

Benign

0.0058

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PhyloP100

-0.32

PrimateAI

Benign

0.41

PROVEAN

Benign

0.35

REVEL

Benign

0.10

Sift

Benign

0.14

Sift4G

Benign

0.46

Polyphen

0.99

Vest4

0.12

MutPred

0.40

Loss of sheet (P = 0.1158)

MVP

0.41

MPC

0.76

ClinPred

0.12

GERP RS

-1.7

Varity_R

0.064

gMVP

0.29

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

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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