Genetic Variant NM_016608.2:c.824G>C (chrX-101553754-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2

The NM_016608.2(ARMCX1):c.824G>C(p.Ser275Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,209,468 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000010 ( 0 hom. 6 hem. )

Consequence

ARMCX1
NM_016608.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.29

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.943

BS2

High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMCX1	NM_016608.2 link	c.824G>C	p.Ser275Thr	missense_variant	Exon 4 of 4	ENST00000372829.8	NP_057692.1	Q9P291A0A024RCI6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMCX1	ENST00000372829.8 link	c.824G>C	p.Ser275Thr	missense_variant	Exon 4 of 4	1	NM_016608.2	ENSP00000361917.3		Q9P291

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

111743

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33923

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000190

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000219

AC:

AN:

182734

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

67212

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000731

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:

0.0000122

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000100

AC:

AN:

1097725

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

363101

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000568

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:

0.0000107

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000268

AC:

AN:

111743

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33923

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.824G>C (p.S275T) alteration is located in exon 4 (coding exon 1) of the ARMCX1 gene. This alteration results from a G to C substitution at nucleotide position 824, causing the serine (S) at amino acid position 275 to be replaced by a threonine (T). 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

Pathogenic

0.77

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.033

MetaRNN

Pathogenic

0.94

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.9

REVEL

Uncertain

0.30

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.010

Polyphen

1.0

Vest4

0.62

MutPred

0.91

Loss of loop (P = 0.1242);

MVP

0.86

MPC

1.5

ClinPred

0.63

GERP RS

3.5

Varity_R

0.74

gMVP

0.72

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