Genetic Variant NM_016608.2:c.418C>A (chrX-101553348-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.418C>A(p.Pro140Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,080,181 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 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: not found (cov: 22)

Exomes 𝑓: 0.000019 ( 0 hom. 9 hem. )

Consequence

ARMCX1
NM_016608.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00300

Publications

0 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=0.0757865).

BS2

High Hemizygotes in GnomAdExome4 at 9 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.418C>A	p.Pro140Thr	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.418C>A	p.Pro140Thr	missense	Exon 4 of 4	ENSP00000361917.3	Q9P291
ARMCX1	ENST00000898854.1		c.418C>A	p.Pro140Thr	missense	Exon 4 of 4	ENSP00000568913.1
ARMCX1	ENST00000898855.1		c.418C>A	p.Pro140Thr	missense	Exon 3 of 3	ENSP00000568914.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1080181

Hom.:

Cov.:

AF XY:

0.0000257

AC XY:

AN XY:

350187

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25871

American (AMR)

AF:

0.00

AC:

AN:

32765

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18004

East Asian (EAS)

AF:

0.00

AC:

AN:

30094

South Asian (SAS)

AF:

0.00

AC:

AN:

50351

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39845

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4024

European-Non Finnish (NFE)

AF:

0.0000228

AC:

AN:

833979

Other (OTH)

AF:

0.0000221

AC:

AN:

45248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions as Germline

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

0.080

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.96

CADD

Benign

5.0

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.028

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.59

M_CAP

Benign

0.0056

MetaRNN

Benign

0.076

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.0030

PrimateAI

Benign

0.43

PROVEAN

Benign

0.48

REVEL

Benign

0.022

Sift

Uncertain

0.015

Sift4G

Uncertain

0.037

Polyphen

0.19

Vest4

0.12

MutPred

0.23

Gain of phosphorylation at P140 (P = 0.0398)

MVP

0.59

MPC

0.86

ClinPred

0.050

GERP RS

0.014

Varity_R

0.075

gMVP

0.60

Mutation Taster

=97/3

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over