Genetic Variant ARMCX2:p.Gly122Trp (chrX-101657225-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_177949.4(ARMCX2):c.364G>T(p.Gly122Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,200,137 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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 0.00012 ( 0 hom., 4 hem., cov: 24)

Exomes 𝑓: 0.0000028 ( 0 hom. 0 hem. )

Consequence

ARMCX2
NM_177949.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.14

Publications

0 publications found

Variant links:

Genes affected

ARMCX2 (HGNC:16869): (armadillo repeat containing X-linked 2) This gene encodes a protein containing a potential N-terminal transmembrane domain and multiple armadillo (arm) repeats. Proteins containing arm repeats are involved in development, maintenance of tissue integrity, and tumorigenesis. This gene is located in a cluster of related genes on chromosome X. There is a pseudogene for this gene on chromosome 7. Alternative splicing in the 5' UTR results in multiple transcript variants encoding the same protein. [provided by RefSeq, Aug 2013]

ARMCX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.048733473).

BS2

High Hemizygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177949.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARMCX2	NM_177949.4	MANE Select	c.364G>T	p.Gly122Trp	missense	Exon 6 of 6	NP_808818.1	Q7L311
ARMCX2	NM_001282231.2		c.364G>T	p.Gly122Trp	missense	Exon 6 of 6	NP_001269160.1	Q7L311
ARMCX2	NM_014782.7		c.364G>T	p.Gly122Trp	missense	Exon 5 of 5	NP_055597.1	Q7L311

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARMCX2	ENST00000356824.9	TSL:1 MANE Select	c.364G>T	p.Gly122Trp	missense	Exon 6 of 6	ENSP00000349281.4	Q7L311
ARMCX2	ENST00000328766.9	TSL:1	c.364G>T	p.Gly122Trp	missense	Exon 5 of 5	ENSP00000331662.5	Q7L311
ARMCX2	ENST00000330154.6	TSL:1	c.364G>T	p.Gly122Trp	missense	Exon 3 of 3	ENSP00000328631.2	Q7L311

Frequencies

GnomAD3 genomes

AF:

0.000124

AC:

AN:

113260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000416

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000920

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

GnomAD2 exomes

AF:

0.00000577

AC:

AN:

173249

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000767

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1086877

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

354897

show subpopulations

African (AFR)

AF:

0.000115

AC:

AN:

26155

American (AMR)

AF:

0.00

AC:

AN:

34401

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18751

East Asian (EAS)

AF:

0.00

AC:

AN:

29961

South Asian (SAS)

AF:

0.00

AC:

AN:

52873

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40277

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4077

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

834913

Other (OTH)

AF:

0.00

AC:

AN:

45469

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

0.000124

AC:

AN:

113260

Hom.:

Cov.:

AF XY:

0.000113

AC XY:

AN XY:

35404

show subpopulations

African (AFR)

AF:

0.000416

AC:

AN:

31241

American (AMR)

AF:

0.0000920

AC:

AN:

10870

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2658

East Asian (EAS)

AF:

0.00

AC:

AN:

3568

South Asian (SAS)

AF:

0.00

AC:

AN:

2785

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6340

Middle Eastern (MID)

AF:

0.00

AC:

AN:

237

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53340

Other (OTH)

AF:

0.00

AC:

AN:

1535

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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:

0.00

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.000261

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

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

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.011

(source)

DANN

Benign

0.17

DEOGEN2

Benign

0.027

FATHMM_MKL

Benign

0.044

LIST_S2

Benign

0.36

M_CAP

Benign

0.010

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

-4.1

PrimateAI

Benign

0.26

PROVEAN

Benign

1.5

REVEL

Benign

0.031

Sift

Benign

0.067

Sift4G

Uncertain

0.059

Polyphen

0.0010

Vest4

0.22

MVP

0.19

MPC

0.44

ClinPred

0.071

GERP RS

-7.9

Varity_R

0.035

gMVP

0.15

Mutation Taster

=100/0

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