rs1935404033

Variant names:

• chrX-101553348-C-A
• rs1935404033
• NM_016608.2:c.418C>A

Variant summary

Our verdict is Likely benign. The variant received -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. 15/21 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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -6 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016608.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMCX1	NM_016608.2	MANE Select	c.418C>A	p.Pro140Thr	missense	Exon 4 of 4	NP_057692.1	Q9P291

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMCX1	ENST00000372829.8	TSL:1 MANE Select	c.418C>A	p.Pro140Thr	missense	Exon 4 of 4	ENSP00000361917.3	Q9P291
	ARMCX1	ENST00000898854.1		c.418C>A	p.Pro140Thr	missense	Exon 4 of 4	ENSP00000568913.1
	ARMCX1	ENST00000898855.1		c.418C>A	p.Pro140Thr	missense	Exon 3 of 3	ENSP00000568914.1

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

African (AFR) AF: 0.00 AC: 0 AN: 25871

American (AMR) AF: 0.00 AC: 0 AN: 32765

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18004

East Asian (EAS) AF: 0.00 AC: 0 AN: 30094

South Asian (SAS) AF: 0.00 AC: 0 AN: 50351

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39845

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4024

European-Non Finnish (NFE) AF: 0.0000228 AC: 19 AN: 833979

Other (OTH) AF: 0.0000221 AC: 1 AN: 45248

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-0.0030
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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1935404033; hg19: chrX-100808331;