X-101616145-C-G

Position:

• chrX-101616145-C-G

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_019007.4(ARMCX6):​c.476G>C​(p.Ser159Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 16)
  • Exomes 𝑓: 0.0000027 (0 hom. 3 hem.)
  • Failed GnomAD Quality Control
• Consequence: ARMCX6 NM_019007.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.18

Genes affected

ARMCX6 (HGNC:26094): (armadillo repeat containing X-linked 6) Predicted to be located in mitochondrial outer membrane. Predicted to be integral component of membrane. Predicted to be active in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ARMCX6 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.36038786).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMCX6	NM_019007.4	c.476G>C	p.Ser159Thr	missense_variant	3/3	ENST00000361910.9	NP_061880.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMCX6	ENST00000361910.9	c.476G>C	p.Ser159Thr	missense_variant	3/3	1	NM_019007.4	ENSP00000354708.4

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD3 exomes AF: 0.00000558 AC: 1 AN: 179106 Hom.: 0 AF XY: 0.0000153 AC XY: 1 AN XY: 65310

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000227

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000274 AC: 3 AN: 1095822 Hom.: 0 Cov.: 30 AF XY: 0.00000830 AC XY: 3 AN XY: 361606

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000238

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 16

ExAC AF: 0.0000330 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 30, 2023

The c.476G>C (p.S159T) alteration is located in exon 4 (coding exon 1) of the ARMCX6 gene. This alteration results from a G to C substitution at nucleotide position 476, causing the serine (S) at amino acid position 159 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T;T;T
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.43	.;.;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.36	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;M;M
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.084
Sift	Uncertain	0.0030	D;D;D
Sift4G	Benign	0.24	T;T;T
Polyphen		0.86	P;P;P
Vest4		0.21
MutPred		0.61		Loss of disorder (P = 0.0612);Loss of disorder (P = 0.0612);Loss of disorder (P = 0.0612);
MVP		0.74
MPC		0.42
ClinPred		0.44	T
GERP RS		2.4
Varity_R		0.31
gMVP		0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs782460352; hg19: chrX-100871135;