Variant 19-19051821-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001199196.2(ARMC6):c.479A>G(p.Asn160Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000551 in 1,613,930 control chromosomes in the GnomAD database, including 1 homozygotes. 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 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 1 hom. )

Consequence

ARMC6
NM_001199196.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.247

Variant links:

Genes affected

ARMC6 (HGNC:25049): (armadillo repeat containing 6) The function of this gene's protein product has not been determined. A related protein in mouse suggests that this protein has a conserved function. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

ARMC6 links:

Genome browser will be placed here

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=0.04376164).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMC6	NM_001199196.2 link	c.479A>G	p.Asn160Ser	missense_variant	5/9	ENST00000535612.6	NP_001186125.1	Q6NXE6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARMC6	ENST00000535612.6 link	c.479A>G	p.Asn160Ser	missense_variant	5/9	1	NM_001199196.2	ENSP00000444156.1		Q6NXE6-1

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000120

AC:

AN:

251016

Hom.:

AF XY:

0.000147

AC XY:

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000705

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1461760

Hom.:

Cov.:

AF XY:

0.0000701

AC XY:

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000396

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152170

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000823

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 25, 2024

The c.479A>G (p.N160S) alteration is located in exon 5 (coding exon 4) of the ARMC6 gene. This alteration results from a A to G substitution at nucleotide position 479, causing the asparagine (N) at amino acid position 160 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

Benign

0.072

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.49

DANN

Benign

0.94

DEOGEN2

Benign

0.026

.;T;T;T;.;T;T;T;T;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.61

.;.;T;T;T;T;T;T;T;T

M_CAP

Benign

0.0061

MetaRNN

Benign

0.044

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

.;L;.;.;.;.;.;.;.;L

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.60

N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.018

Sift

Benign

0.49

T;T;T;T;T;T;T;T;T;T

Sift4G

Benign

0.42

T;T;T;T;T;T;T;T;T;T

Polyphen

0.0080

.;B;.;.;.;.;.;.;.;B

Vest4

0.11

MVP

0.28

MPC

0.18

ClinPred

0.0045

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.018

gMVP

0.039

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over