X-101625007-G-C

Variant names:

• chrX-101625007-G-C
• NM_177947.3:c.28G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_177947.3(ARMCX3):​c.28G>C​(p.Val10Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ARMCX3 NM_177947.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.42

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4115008).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMCX3	NM_177947.3	c.28G>C	p.Val10Leu	missense_variant	Exon 5 of 5	ENST00000471229.7	NP_808816.1
ARMCX3	NM_016607.4	c.28G>C	p.Val10Leu	missense_variant	Exon 5 of 5		NP_057691.1
ARMCX3	NM_177948.3	c.28G>C	p.Val10Leu	missense_variant	Exon 5 of 5		NP_808817.1
ARMCX3	XM_005262141.4	c.28G>C	p.Val10Leu	missense_variant	Exon 5 of 5		XP_005262198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMCX3	ENST00000471229.7	c.28G>C	p.Val10Leu	missense_variant	Exon 5 of 5	1	NM_177947.3	ENSP00000454483.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 01, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.28G>C (p.V10L) alteration is located in exon 5 (coding exon 1) of the ARMCX3 gene. This alteration results from a G to C substitution at nucleotide position 28, causing the valine (V) at amino acid position 10 to be replaced by a leucine (L). 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	Uncertain	0.44
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.058	T;T;T;.;T
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.81	.;.;T;T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.41	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M;.;.;M
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-1.3	N;N;N;N;N
REVEL	Benign	0.060
Sift	Uncertain	0.0040	D;D;D;D;D
Sift4G	Uncertain	0.017	D;D;D;D;D
Polyphen		0.93	P;P;.;.;P
Vest4		0.44
MutPred		0.44		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP		0.82
MPC		1.8
ClinPred		0.86	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.29
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-100879997;