X-102602626-C-T

Variant names:

• chrX-102602626-C-T
• rs923659718
• NM_001168478.2:c.485C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001168478.2(ARMCX5):​c.485C>T​(p.Ser162Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,208,277 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 0.0000090 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: ARMCX5 NM_001168478.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.341
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03417617).

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.485C>T	p.Ser162Phe	missense	Exon 4 of 4	NP_001161950.1	Q6P1M9
	ARMCX5	NM_001168479.2		c.485C>T	p.Ser162Phe	missense	Exon 6 of 6	NP_001161951.1	Q6P1M9
	ARMCX5	NM_001168480.2		c.485C>T	p.Ser162Phe	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.485C>T	p.Ser162Phe	missense	Exon 4 of 4	ENSP00000473737.2	Q6P1M9
	ARMCX5	ENST00000479502.2	TSL:1	c.485C>T	p.Ser162Phe	missense	Exon 3 of 3	ENSP00000474470.2	Q6P1M9
	ENSG00000271147	ENST00000466616.6	TSL:1	n.466+649C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000898 AC: 1 AN: 111313 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000328

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1096964 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 362394

African (AFR) AF: 0.0000758 AC: 2 AN: 26378

American (AMR) AF: 0.00 AC: 0 AN: 35203

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19380

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 54124

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40525

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 840970

Other (OTH) AF: 0.00 AC: 0 AN: 46054

GnomAD4 genome AF: 0.00000898 AC: 1 AN: 111313 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33501

African (AFR) AF: 0.0000328 AC: 1 AN: 30524

American (AMR) AF: 0.00 AC: 0 AN: 10530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2641

East Asian (EAS) AF: 0.00 AC: 0 AN: 3534

South Asian (SAS) AF: 0.00 AC: 0 AN: 2612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53030

Other (OTH) AF: 0.00 AC: 0 AN: 1489

Alfa AF: 0.000142 Hom.: 1

Bravo AF: 0.0000189

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	0.089
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.92
CADD	Benign	10
DANN	Benign	0.73
DEOGEN2	Benign	0.026	T
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.29	N
PhyloP100		0.34
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.017
Sift	Benign	0.77	T
Sift4G	Benign	0.18	T
Polyphen		0.0010	B
Vest4		0.082
MutPred		0.28		Loss of phosphorylation at S162 (P = 0.0149)
MVP		0.068
MPC		0.13
ClinPred		0.027	T
GERP RS		-0.25
Varity_R		0.069
gMVP		0.10
Mutation Taster		=97/3	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: rs923659718; hg19: chrX-101857554;