NM_001168478.2:c.448C>T

Variant names:

• chrX-102602589-C-T
• rs750414266
• NM_001168478.2:c.448C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001168478.2(ARMCX5):​c.448C>T​(p.Pro150Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000729 in 1,097,448 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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: 23)
  • Exomes 𝑓: 0.0000073 (0 hom. 3 hem.)
• Consequence: ARMCX5 NM_001168478.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.50
• Publications: 0 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.032454878).
• BS2: High Hemizygotes in GnomAdExome4 at 3 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.448C>T	p.Pro150Ser	missense	Exon 4 of 4	NP_001161950.1	Q6P1M9
	ARMCX5	NM_001168479.2		c.448C>T	p.Pro150Ser	missense	Exon 6 of 6	NP_001161951.1	Q6P1M9
	ARMCX5	NM_001168480.2		c.448C>T	p.Pro150Ser	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.448C>T	p.Pro150Ser	missense	Exon 4 of 4	ENSP00000473737.2	Q6P1M9
	ARMCX5	ENST00000479502.2	TSL:1	c.448C>T	p.Pro150Ser	missense	Exon 3 of 3	ENSP00000474470.2	Q6P1M9
	ENSG00000271147	ENST00000466616.6	TSL:1	n.466+612C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.0000164 AC: 3 AN: 182755 AF XY: 0.0000148

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000729 AC: 8 AN: 1097448 Hom.: 0 Cov.: 31 AF XY: 0.00000827 AC XY: 3 AN XY: 362830

African (AFR) AF: 0.00 AC: 0 AN: 26384

American (AMR) AF: 0.00 AC: 0 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19378

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

South Asian (SAS) AF: 0.000148 AC: 8 AN: 54125

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40530

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841412

Other (OTH) AF: 0.00 AC: 0 AN: 46076

GnomAD4 genome Cov.: 23

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	0.085
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.0060
DANN	Benign	0.099
DEOGEN2	Benign	0.018	T
FATHMM_MKL	Benign	0.042	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.032	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PhyloP100		-1.5
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.013
Sift	Benign	0.71	T
Sift4G	Benign	0.52	T
Polyphen		0.020	B
Vest4		0.029
MutPred		0.17		Gain of phosphorylation at P150 (P = 0.0043)
MVP		0.082
MPC		0.12
ClinPred		0.027	T
GERP RS		-0.47
Varity_R		0.026
gMVP		0.091
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: rs750414266; hg19: chrX-101857517;