X-101616590-C-A

Position:

• chrX-101616590-C-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_019007.4(ARMCX6):​c.31G>T​(p.Ala11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000456 in 1,096,223 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000046 (0 hom. 2 hem.)
• Consequence: ARMCX6 NM_019007.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.03

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 -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMCX6	NM_019007.4	c.31G>T	p.Ala11Ser	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.31G>T	p.Ala11Ser	missense_variant	3/3	1	NM_019007.4	ENSP00000354708.4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000456 AC: 5 AN: 1096223 Hom.: 0 Cov.: 31 AF XY: 0.00000553 AC XY: 2 AN XY: 361735

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: 0.00000595

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000149 AC: 1

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

Jun 10, 2024

The c.31G>T (p.A11S) alteration is located in exon 4 (coding exon 1) of the ARMCX6 gene. This alteration results from a G to T substitution at nucleotide position 31, causing the alanine (A) at amino acid position 11 to be replaced by a serine (S). 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	Uncertain	0.43
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T;T;T
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.67	.;.;T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Benign	1.0	L;L;L
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-1.0	N;N;N
REVEL	Benign	0.096
Sift	Uncertain	0.0090	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.44
MVP		0.91
MPC		0.73
ClinPred		0.85	D
GERP RS		3.7
Varity_R		0.23
gMVP		0.058

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: rs150079861; hg19: chrX-100871580;