NM_001168478.2:c.489T>G

Variant names:

• chrX-102602630-T-G
• rs201641747
• NM_001168478.2:c.489T>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001168478.2(ARMCX5):​c.489T>G​(p.Ser163Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000353 in 1,208,158 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 129 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: 𝑓 0.00020 (0 hom., 5 hem., cov: 23)
  • Exomes 𝑓: 0.00037 (0 hom. 124 hem.)
• Consequence: ARMCX5 NM_001168478.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23
• Publications: 1 publications found

Genes affected

ARMCX5 (HGNC:25772): (armadillo repeat containing X-linked 5)

ENSG00000271147 (HGNC:):

ARMCX5-GPRASP2 (HGNC:42000): (ARMCX5-GPRASP2 readthrough) This locus represents naturally occurring readthrough transcription among the adjacent armadillo repeat containing, X-linked 5 (ARMCX5), G protein-coupled receptor associated sorting proteins 1 and 2 (GPRASP1 and GPRASP2), basic helix-loop-helix family member b9 (BHLHB9), and long intergenic non-protein coding RNA 630 (LINC00630) genes on chromosome X. Transcripts may make use of multiple alternative promoters and polyadenylation signals in this region. Readthrough transcripts may produce proteins identical to the proteins encoded by GPRASP2 or BHLHB9. [provided by RefSeq, Apr 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.07043135).
• BS2: High Hemizygotes in GnomAd4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001168478.2. 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
	ARMCX5	NM_001168478.2	MANE Select	c.489T>G	p.Ser163Arg	missense	Exon 4 of 4	NP_001161950.1	Q6P1M9
	ARMCX5	NM_001168479.2		c.489T>G	p.Ser163Arg	missense	Exon 6 of 6	NP_001161951.1	Q6P1M9
	ARMCX5	NM_001168480.2		c.489T>G	p.Ser163Arg	missense	Exon 6 of 6	NP_001161952.1	Q6P1M9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMCX5	ENST00000473968.7	TSL:2 MANE Select	c.489T>G	p.Ser163Arg	missense	Exon 4 of 4	ENSP00000473737.2	Q6P1M9
	ARMCX5	ENST00000479502.2	TSL:1	c.489T>G	p.Ser163Arg	missense	Exon 3 of 3	ENSP00000474470.2	Q6P1M9
	ENSG00000271147	ENST00000466616.6	TSL:1	n.466+653T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000198 AC: 22 AN: 111014 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000985

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: 0.000359

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000137 AC: 25 AN: 182751 AF XY: 0.000178

Gnomad AFR exome AF: 0.000228

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000258

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000369 AC: 405 AN: 1097144 Hom.: 0 Cov.: 31 AF XY: 0.000342 AC XY: 124 AN XY: 362556

African (AFR) AF: 0.000114 AC: 3 AN: 26373

American (AMR) AF: 0.0000284 AC: 1 AN: 35203

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19381

East Asian (EAS) AF: 0.00 AC: 0 AN: 30198

South Asian (SAS) AF: 0.00 AC: 0 AN: 54126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.000464 AC: 390 AN: 841140

Other (OTH) AF: 0.000239 AC: 11 AN: 46059

GnomAD4 genome AF: 0.000198 AC: 22 AN: 111014 Hom.: 0 Cov.: 23 AF XY: 0.000150 AC XY: 5 AN XY: 33254

African (AFR) AF: 0.0000985 AC: 3 AN: 30452

American (AMR) AF: 0.00 AC: 0 AN: 10511

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3506

South Asian (SAS) AF: 0.00 AC: 0 AN: 2594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.000359 AC: 19 AN: 52928

Other (OTH) AF: 0.00 AC: 0 AN: 1488

Alfa AF: 0.000331 Hom.: 16

Bravo AF: 0.000170

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000346 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000446 AC: 3

ExAC AF: 0.000181 AC: 22

EpiCase AF: 0.000436

EpiControl AF: 0.000178

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	0.14
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	17
DANN	Benign	0.58
DEOGEN2	Benign	0.028	T
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.2
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.41	N
REVEL	Benign	0.051
Sift	Benign	0.54	T
Sift4G	Benign	0.065	T
Polyphen		0.15	B
Vest4		0.19
MutPred		0.18		Loss of phosphorylation at S163 (P = 0.0174)
MVP		0.30
MPC		0.17
ClinPred		0.016	T
GERP RS		3.6
Varity_R		0.19
gMVP		0.055
Mutation Taster		=100/0	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: rs201641747; hg19: chrX-101857558;