X-101553348-C-A

Position:

• chrX-101553348-C-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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. 14/20 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00300

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0757865).
• BS2: High Hemizygotes in GnomAdExome4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMCX1	NM_016608.2	c.418C>A	p.Pro140Thr	missense_variant	4/4	ENST00000372829.8	NP_057692.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMCX1	ENST00000372829.8	c.418C>A	p.Pro140Thr	missense_variant	4/4	1	NM_016608.2	ENSP00000361917.3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.0000185 AC: 20 AN: 1080181 Hom.: 0 Cov.: 32 AF XY: 0.0000257 AC XY: 9 AN XY: 350187

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: 0.0000228

Gnomad4 OTH exome AF: 0.0000221

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 20, 2024

The c.418C>A (p.P140T) alteration is located in exon 4 (coding exon 1) of the ARMCX1 gene. This alteration results from a C to A substitution at nucleotide position 418, causing the proline (P) at amino acid position 140 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	Benign	0.080
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.0
DANN	Benign	0.97
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.48	N
REVEL	Benign	0.022
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.037	D
Polyphen		0.19	B
Vest4		0.12
MutPred		0.23		Gain of phosphorylation at P140 (P = 0.0398);
MVP		0.59
MPC		0.86
ClinPred		0.050	T
GERP RS		0.014
Varity_R		0.075
gMVP		0.60

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

Other links and lift over

dbSNP: rs1935404033; hg19: chrX-100808331;