Variant X-101625760-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_177947.3(ARMCX3):c.781C>T(p.Leu261Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000937 in 1,066,671 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 9.4e-7 ( 0 hom. 0 hem. )

Consequence

ARMCX3
NM_177947.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.682

Variant links:

Genes affected

ARMCX3 (HGNC:24065): (armadillo repeat containing X-linked 3) This gene encodes a member of the ALEX family of proteins which may play a role in tumor suppression. The encoded protein contains a potential N-terminal transmembrane domain and a single Armadillo (arm) repeat. Other proteins containing the arm repeat are involved in development, maintenance of tissue integrity, and tumorigenesis. This gene is closely localized with other family members on the X chromosome. Three transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

ARMCX3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14580101).

BP6

Variant X-101625760-C-T is Benign according to our data. Variant chrX-101625760-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2339295.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ARMCX3	NM_177947.3 linkuse as main transcript	c.781C>T	p.Leu261Phe	missense_variant	5/5	ENST00000471229.7	NP_808816.1
ARMCX3	NM_016607.4 linkuse as main transcript	c.781C>T	p.Leu261Phe	missense_variant	5/5		NP_057691.1
ARMCX3	NM_177948.3 linkuse as main transcript	c.781C>T	p.Leu261Phe	missense_variant	5/5		NP_808817.1
ARMCX3	XM_005262141.4 linkuse as main transcript	c.781C>T	p.Leu261Phe	missense_variant	5/5		XP_005262198.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ARMCX3	ENST00000471229.7 linkuse as main transcript	c.781C>T	p.Leu261Phe	missense_variant	5/5	1	NM_177947.3	ENSP00000454483	P1
ARMCX3	ENST00000341189.8 linkuse as main transcript	c.781C>T	p.Leu261Phe	missense_variant	5/5	1		ENSP00000340672	P1
ARMCX3	ENST00000537169.1 linkuse as main transcript	c.781C>T	p.Leu261Phe	missense_variant	5/5	1		ENSP00000439032	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.37e-7

AC:

AN:

1066671

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

346595

show subpopulations

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0084

T;T;T

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.67

.;.;T

M_CAP

Benign

0.083

MetaRNN

Benign

0.15

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.75

N;N;N

MutationTaster

Benign

0.64

N;N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.67

N;N;N

REVEL

Benign

0.10

Sift

Benign

0.096

T;T;T

Sift4G

Benign

0.063

T;T;T

Polyphen

0.0010

B;B;B

Vest4

0.087

MutPred

0.62

Gain of methylation at K260 (P = 0.0269);Gain of methylation at K260 (P = 0.0269);Gain of methylation at K260 (P = 0.0269);

MVP

0.97

MPC

1.0

ClinPred

0.39

GERP RS

3.9

Varity_R

0.13

gMVP

0.29

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over