rs375844900

Variant names:

• chrX-101625338-C-A
• rs375844900
• NM_177947.3:c.359C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-101625338-C-A
• chrX-101625338-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_177947.3(ARMCX3):​c.359C>A​(p.Pro120His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,209,588 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000016 (0 hom. 2 hem.)
• Consequence: ARMCX3 NM_177947.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177947.3. 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
	ARMCX3	NM_177947.3	MANE Select	c.359C>A	p.Pro120His	missense	Exon 5 of 5	NP_808816.1	Q9UH62
	ARMCX3	NM_016607.4		c.359C>A	p.Pro120His	missense	Exon 5 of 5	NP_057691.1	Q9UH62
	ARMCX3	NM_177948.3		c.359C>A	p.Pro120His	missense	Exon 5 of 5	NP_808817.1	Q9UH62

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMCX3	ENST00000471229.7	TSL:1 MANE Select	c.359C>A	p.Pro120His	missense	Exon 5 of 5	ENSP00000454483.1	Q9UH62
	ARMCX3	ENST00000341189.8	TSL:1	c.359C>A	p.Pro120His	missense	Exon 5 of 5	ENSP00000340672.4	Q9UH62
	ARMCX3	ENST00000537169.1	TSL:1	c.359C>A	p.Pro120His	missense	Exon 5 of 5	ENSP00000439032.1	Q9UH62

Frequencies

GnomAD3 genomes AF: 0.0000267 AC: 3 AN: 112430 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000563

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000111 AC: 2 AN: 179518 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000250

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 18 AN: 1097158 Hom.: 0 Cov.: 31 AF XY: 0.00000552 AC XY: 2 AN XY: 362588

African (AFR) AF: 0.00 AC: 0 AN: 26374

American (AMR) AF: 0.00 AC: 0 AN: 35085

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19299

East Asian (EAS) AF: 0.00 AC: 0 AN: 30201

South Asian (SAS) AF: 0.00 AC: 0 AN: 53864

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40497

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4130

European-Non Finnish (NFE) AF: 0.0000202 AC: 17 AN: 841664

Other (OTH) AF: 0.0000217 AC: 1 AN: 46044

GnomAD4 genome AF: 0.0000267 AC: 3 AN: 112430 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34592

African (AFR) AF: 0.00 AC: 0 AN: 30955

American (AMR) AF: 0.00 AC: 0 AN: 10711

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3567

South Asian (SAS) AF: 0.00 AC: 0 AN: 2718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000563 AC: 3 AN: 53266

Other (OTH) AF: 0.00 AC: 0 AN: 1507

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

ExAC AF: 0.00000824 AC: 1

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	0.31
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.5	L
PhyloP100		3.3
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.20
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.55
MVP		0.99
MPC		2.2
ClinPred		0.93	D
GERP RS		4.1
Varity_R		0.57
gMVP		0.68
Mutation Taster		=87/13	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: rs375844900; hg19: chrX-100880328; COSMIC: COSV100362258; COSMIC: COSV100362258;