NM_001256155.3:c.1504G>A

Variant names:

• chrX-101490093-G-A
• rs782351023
• NM_001256155.3:c.1504G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001256155.3(ARMCX4):​c.1504G>A​(p.Glu502Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 1,154,548 control chromosomes in the GnomAD database, including 3 homozygotes. There are 849 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., 46 hem., cov: 24)
  • Exomes 𝑓: 0.0025 (3 hom. 803 hem.)
• Consequence: ARMCX4 NM_001256155.3 missense
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: 1.66
• Publications: 4 publications found

Genes affected

ARMCX4 (HGNC:28615): (armadillo repeat containing X-linked 4) The product of this gene belongs to the armadillo repeat-containing family of proteins, which interact with other proteins in a variety of cellular processes. The function of this family member is currently unknown. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.035895377).
• BP6: Variant X-101490093-G-A is Benign according to our data. Variant chrX-101490093-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1206017.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Hemizygotes in GnomAd4 at 46 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256155.3. 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
	ARMCX4	NM_001256155.3	MANE Select	c.1504G>A	p.Glu502Lys	missense	Exon 6 of 6	NP_001243084.2	Q5H9R4-1
	ARMCX4	NR_028407.3		n.1533+778G>A		intron	N/A
	ARMCX4	NR_045861.2		n.1237+778G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMCX4	ENST00000423738.5	TSL:5 MANE Select	c.1504G>A	p.Glu502Lys	missense	Exon 6 of 6	ENSP00000404304.3	Q5H9R4-1
	ARMCX4	ENST00000354842.5	TSL:1	n.726+778G>A		intron	N/A	ENSP00000423927.2	A0A8J9A6E2
	ARMCX4	ENST00000433011.6	TSL:1	n.726+778G>A		intron	N/A	ENSP00000424452.2	A0A8J9A6E2

Frequencies

GnomAD3 genomes AF: 0.00155 AC: 174 AN: 112266 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000937

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000163

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00271

Gnomad OTH AF: 0.00267

GnomAD2 exomes AF: 0.00162 AC: 158 AN: 97802 AF XY: 0.00148

Gnomad AFR exome AF: 0.000390

Gnomad AMR exome AF: 0.00135

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000246

Gnomad NFE exome AF: 0.00316

Gnomad OTH exome AF: 0.00163

GnomAD4 exome AF: 0.00249 AC: 2593 AN: 1042224 Hom.: 3 Cov.: 37 AF XY: 0.00235 AC XY: 803 AN XY: 341264

African (AFR) AF: 0.000361 AC: 9 AN: 24916

American (AMR) AF: 0.00125 AC: 35 AN: 27910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18641

East Asian (EAS) AF: 0.00 AC: 0 AN: 27133

South Asian (SAS) AF: 0.000200 AC: 10 AN: 49888

European-Finnish (FIN) AF: 0.000232 AC: 6 AN: 25847

Middle Eastern (MID) AF: 0.00147 AC: 6 AN: 4087

European-Non Finnish (NFE) AF: 0.00297 AC: 2437 AN: 819494

Other (OTH) AF: 0.00203 AC: 90 AN: 44308

GnomAD4 genome AF: 0.00156 AC: 175 AN: 112324 Hom.: 0 Cov.: 24 AF XY: 0.00133 AC XY: 46 AN XY: 34470

African (AFR) AF: 0.000484 AC: 15 AN: 30987

American (AMR) AF: 0.000936 AC: 10 AN: 10683

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3555

South Asian (SAS) AF: 0.00 AC: 0 AN: 2691

European-Finnish (FIN) AF: 0.000163 AC: 1 AN: 6141

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00273 AC: 145 AN: 53203

Other (OTH) AF: 0.00264 AC: 4 AN: 1517

Alfa AF: 0.00115 Hom.: 16

Bravo AF: 0.00155

TwinsUK AF: 0.00351 AC: 13

ALSPAC AF: 0.00277 AC: 8

ExAC AF: 0.000415 AC: 7

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.2
DANN	Benign	0.96
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.52	T
M_CAP	Pathogenic	0.68	D
MetaRNN	Benign	0.036	T
MetaSVM	Benign	-0.95	T
PhyloP100		1.7
PrimateAI	Benign	0.34	T
REVEL	Benign	0.097
Sift4G	Benign	0.073	T
Vest4		0.24
MVP		0.26
ClinPred		0.99	D
GERP RS		4.8
gMVP		0.31
Mutation Taster		=97/3	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: rs782351023; hg19: chrX-100745080;