Genetic Variant ARMCX4:p.Thr904Lys (chrX-101491300-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001256155.3(ARMCX4):c.2711C>A(p.Thr904Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000173 in 1,154,342 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 27)

Exomes 𝑓: 0.000017 ( 0 hom. 10 hem. )

Consequence

ARMCX4
NM_001256155.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.288

Publications

0 publications found

Variant links:

Genes affected

ARMCX4 (HGNC:28615): (armadillo repeat containing X-linked 4) The product of this gene belongs to the armadillo repeat-containing family of proteins, which interact with other proteins in a variety of cellular processes. The function of this family member is currently unknown. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

ARMCX4 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.113579035).

BP6

Variant X-101491300-C-A is Benign according to our data. Variant chrX-101491300-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2661062.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 10 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256155.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARMCX4	NM_001256155.3	MANE Select	c.2711C>A	p.Thr904Lys	missense	Exon 6 of 6	NP_001243084.2	Q5H9R4-1
ARMCX4	NR_028407.3		n.1533+1985C>A		intron	N/A
ARMCX4	NR_045861.2		n.1237+1985C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ARMCX4	ENST00000423738.5	TSL:5 MANE Select	c.2711C>A	p.Thr904Lys	missense	Exon 6 of 6	ENSP00000404304.3	Q5H9R4-1
ARMCX4	ENST00000354842.5	TSL:1	n.726+1985C>A		intron	N/A	ENSP00000423927.2	A0A8J9A6E2
ARMCX4	ENST00000433011.6	TSL:1	n.726+1985C>A		intron	N/A	ENSP00000424452.2	A0A8J9A6E2

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112186

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:

0.000281

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000658

GnomAD2 exomes

AF:

0.0000511

AC:

AN:

97912

AF XY:

0.000109

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000518

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000383

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000260

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000173

AC:

AN:

1042100

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

341272

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24886

American (AMR)

AF:

0.00

AC:

AN:

27905

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18643

East Asian (EAS)

AF:

0.000258

AC:

AN:

27130

South Asian (SAS)

AF:

0.0000401

AC:

AN:

49874

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25890

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4088

European-Non Finnish (NFE)

AF:

0.00000854

AC:

AN:

819379

Other (OTH)

AF:

0.0000451

AC:

AN:

44305

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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:

0.0000178

AC:

AN:

112242

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34580

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30940

American (AMR)

AF:

0.00

AC:

AN:

10742

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2656

East Asian (EAS)

AF:

0.000282

AC:

AN:

3543

South Asian (SAS)

AF:

0.00

AC:

AN:

2700

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53113

Other (OTH)

AF:

0.000649

AC:

AN:

1540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.63

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.32

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

PhyloP100

0.29

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.0

REVEL

Benign

0.019

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0060

Vest4

0.12

MVP

0.088

ClinPred

0.099

GERP RS

2.7

gMVP

0.35

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over