rs142274849

Variant names:

• chrX-101552945-G-A
• rs142274849
• NM_016608.2:c.15G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_016608.2(ARMCX1):​c.15G>A​(p.Arg5Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00475 in 1,208,561 control chromosomes in the GnomAD database, including 6 homozygotes. There are 1,815 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (0 hom., 76 hem., cov: 22)
  • Exomes 𝑓: 0.0049 (6 hom. 1739 hem.)
• Consequence: ARMCX1 NM_016608.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.456
• Publications: 4 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant X-101552945-G-A is Benign according to our data. Variant chrX-101552945-G-A is described in ClinVar as Benign. ClinVar VariationId is 769182.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.456 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 76 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.15G>A	p.Arg5Arg	synonymous	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.15G>A	p.Arg5Arg	synonymous	Exon 4 of 4	ENSP00000361917.3	Q9P291
	ARMCX1	ENST00000898854.1		c.15G>A	p.Arg5Arg	synonymous	Exon 4 of 4	ENSP00000568913.1
	ARMCX1	ENST00000898855.1		c.15G>A	p.Arg5Arg	synonymous	Exon 3 of 3	ENSP00000568914.1

Frequencies

GnomAD3 genomes AF: 0.00305 AC: 342 AN: 112088 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.000648

Gnomad AMI AF: 0.0117

Gnomad AMR AF: 0.00558

Gnomad ASJ AF: 0.00151

Gnomad EAS AF: 0.000282

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000492

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00445

Gnomad OTH AF: 0.00661

GnomAD2 exomes AF: 0.00310 AC: 555 AN: 178777 AF XY: 0.00330

Gnomad AFR exome AF: 0.000457

Gnomad AMR exome AF: 0.00402

Gnomad ASJ exome AF: 0.00155

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000764

Gnomad NFE exome AF: 0.00490

Gnomad OTH exome AF: 0.00588

GnomAD4 exome AF: 0.00492 AC: 5399 AN: 1096419 Hom.: 6 Cov.: 31 AF XY: 0.00480 AC XY: 1739 AN XY: 361985

African (AFR) AF: 0.000531 AC: 14 AN: 26372

American (AMR) AF: 0.00430 AC: 151 AN: 35085

Ashkenazi Jewish (ASJ) AF: 0.00145 AC: 28 AN: 19247

East Asian (EAS) AF: 0.00 AC: 0 AN: 30195

South Asian (SAS) AF: 0.0000372 AC: 2 AN: 53695

European-Finnish (FIN) AF: 0.000668 AC: 27 AN: 40427

Middle Eastern (MID) AF: 0.000485 AC: 2 AN: 4126

European-Non Finnish (NFE) AF: 0.00592 AC: 4980 AN: 841254

Other (OTH) AF: 0.00424 AC: 195 AN: 46018

GnomAD4 genome AF: 0.00306 AC: 343 AN: 112142 Hom.: 0 Cov.: 22 AF XY: 0.00222 AC XY: 76 AN XY: 34300

African (AFR) AF: 0.000647 AC: 20 AN: 30917

American (AMR) AF: 0.00557 AC: 59 AN: 10591

Ashkenazi Jewish (ASJ) AF: 0.00151 AC: 4 AN: 2651

East Asian (EAS) AF: 0.000283 AC: 1 AN: 3538

South Asian (SAS) AF: 0.00 AC: 0 AN: 2680

European-Finnish (FIN) AF: 0.000492 AC: 3 AN: 6093

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00447 AC: 238 AN: 53237

Other (OTH) AF: 0.00653 AC: 10 AN: 1532

Alfa AF: 0.00381 Hom.: 27

Bravo AF: 0.00365

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.4
DANN	Benign	0.70
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

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: rs142274849; hg19: chrX-100807928; COSMIC: COSV100863169;