Variant 10-122454827-A-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001099667.3(ARMS2):c.100A>T(p.Ile34Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ARMS2
NM_001099667.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.573

Variant links:

Genes affected

ARMS2 (HGNC:32685): (age-related maculopathy susceptibility 2) This gene encodes a small secreted protein specific to primates. This protein is a component of the choroidal extracellular matrix of the eye. Mutations in this gene are associated with age-related macular degeneration. [provided by RefSeq, Sep 2017]

ARMS2 links:

ENSG00000285955 (HGNC:):

ENSG00000285955 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=0.12404412).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARMS2	NM_001099667.3 linkuse as main transcript	c.100A>T	p.Ile34Phe	missense_variant	1/2	ENST00000528446.1	NP_001093137.1	P0C7Q2
LOC105378525	XR_946382.3 linkuse as main transcript	n.1874+3668T>A		intron_variant
LOC105378525	XR_946383.3 linkuse as main transcript	n.1852+3668T>A		intron_variant
LOC105378525	XR_946384.3 linkuse as main transcript	n.1601+3668T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ARMS2	ENST00000528446.1 linkuse as main transcript	c.100A>T	p.Ile34Phe	missense_variant	1/2	1	NM_001099667.3	ENSP00000436682.1	P0C7Q2
ENSG00000285955	ENST00000647969.1 linkuse as main transcript	n.182+3668T>A		intron_variant
ENSG00000285955	ENST00000650300.1 linkuse as main transcript	n.1852+3668T>A		intron_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461710

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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: 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

Jul 31, 2024

The c.100A>T (p.I34F) alteration is located in exon 1 (coding exon 1) of the ARMS2 gene. This alteration results from a A to T substitution at nucleotide position 100, causing the isoleucine (I) at amino acid position 34 to be replaced by a phenylalanine (F). 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

0.14

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.1

DANN

Benign

0.75

DEOGEN2

Benign

0.047

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.38

M_CAP

Benign

0.0037

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.058

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.95

Vest4

0.15

MutPred

0.23

Loss of sheet (P = 0.0315);

MVP

0.014

MPC

1.4

ClinPred

0.30

GERP RS

-0.54

Varity_R

0.36

gMVP

0.020

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