Variant X-101625338-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000471229.7(ARMCX3):c.359C>A(p.Pro120His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,209,588 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000016 ( 0 hom. 2 hem. )

Consequence

ARMCX3
ENST00000471229.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.33

Variant links:

Genes affected

ARMCX3 (HGNC:24065): (armadillo repeat containing X-linked 3) This gene encodes a member of the ALEX family of proteins which may play a role in tumor suppression. The encoded protein contains a potential N-terminal transmembrane domain and a single Armadillo (arm) repeat. 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 on the X chromosome. Three transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

ARMCX3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMCX3	NM_177947.3 linkuse as main transcript	c.359C>A	p.Pro120His	missense_variant	5/5	ENST00000471229.7	NP_808816.1	Q9UH62A0A024RCF9
ARMCX3	NM_016607.4 linkuse as main transcript	c.359C>A	p.Pro120His	missense_variant	5/5		NP_057691.1	Q9UH62A0A024RCF9
ARMCX3	NM_177948.3 linkuse as main transcript	c.359C>A	p.Pro120His	missense_variant	5/5		NP_808817.1	Q9UH62A0A024RCF9
ARMCX3	XM_005262141.4 linkuse as main transcript	c.359C>A	p.Pro120His	missense_variant	5/5		XP_005262198.1	Q9UH62A0A024RCF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARMCX3	ENST00000471229.7 linkuse as main transcript	c.359C>A	p.Pro120His	missense_variant	5/5	1	NM_177947.3	ENSP00000454483.1	Q9UH62
ARMCX3	ENST00000341189.8 linkuse as main transcript	c.359C>A	p.Pro120His	missense_variant	5/5	1		ENSP00000340672.4	Q9UH62
ARMCX3	ENST00000537169.1 linkuse as main transcript	c.359C>A	p.Pro120His	missense_variant	5/5	1		ENSP00000439032.1	Q9UH62

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112430

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34592

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000563

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000111

AC:

AN:

179518

Hom.:

AF XY:

0.00

AC XY:

AN XY:

65038

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000250

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1097158

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

362588

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000202

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112430

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34592

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000563

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 13, 2023

The c.359C>A (p.P120H) alteration is located in exon 5 (coding exon 1) of the ARMCX3 gene. This alteration results from a C to A substitution at nucleotide position 359, causing the proline (P) at amino acid position 120 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

T;T;T

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.56

.;.;T

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.66

D;D;D

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.5

L;L;L

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-4.4

D;D;D

REVEL

Benign

0.20

Sift

Uncertain

0.0060

D;D;D

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.55

MVP

0.99

MPC

2.2

ClinPred

0.93

GERP RS

4.1

Varity_R

0.57

gMVP

0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over