Variant 8-65604471-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000276569.8(ARMC1):c.772G>C(p.Val258Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ARMC1
ENST00000276569.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.83

Variant links:

Genes affected

ARMC1 (HGNC:17684): (armadillo repeat containing 1) Predicted to enable metal ion binding activity. Involved in intracellular distribution of mitochondria. Located in cytosol and mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ARMC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13433436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMC1	NM_018120.6 linkuse as main transcript	c.772G>C	p.Val258Leu	missense_variant	7/7	ENST00000276569.8	NP_060590.1	Q9NVT9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARMC1	ENST00000276569.8 linkuse as main transcript	c.772G>C	p.Val258Leu	missense_variant	7/7	1	NM_018120.6	ENSP00000276569.3	Q9NVT9-1
ARMC1	ENST00000458464.3 linkuse as main transcript	c.466G>C	p.Val156Leu	missense_variant	6/6	2		ENSP00000388572.2	Q9NVT9-2
ARMC1	ENST00000528721.5 linkuse as main transcript	n.*273G>C		non_coding_transcript_exon_variant	6/6	2		ENSP00000434297.1	E9PR92
ARMC1	ENST00000528721.5 linkuse as main transcript	n.*273G>C		3_prime_UTR_variant	6/6	2		ENSP00000434297.1	E9PR92

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727240

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000468

Hom.:

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

Sep 01, 2021

The c.772G>C (p.V258L) alteration is located in exon 7 (coding exon 6) of the ARMC1 gene. This alteration results from a G to C substitution at nucleotide position 772, causing the valine (V) at amino acid position 258 to be replaced by a leucine (L). 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

0.34

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.028

T;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.055

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.73

N;N

REVEL

Benign

0.056

Sift

Benign

0.21

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.0060

B;.

Vest4

0.076

MutPred

0.14

Gain of helix (P = 0.0117);.;

MVP

0.18

MPC

0.46

ClinPred

0.50

GERP RS

4.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.076

gMVP

0.23

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

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