10-122454972-C-T

Variant names:

• chr10-122454972-C-T
• NM_001099667.3:c.245C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001099667.3(ARMS2):​c.245C>T​(p.Ser82Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ARMS2 NM_001099667.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.59

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]

LOC105378525 (HGNC:):

ENSG00000285955 (HGNC:58122):

ACMG classification

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=0.06571522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ARMS2	NM_001099667.3	c.245C>T	p.Ser82Phe	missense_variant	Exon 1 of 2	ENST00000528446.1	NP_001093137.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ARMS2	ENST00000528446.1	c.245C>T	p.Ser82Phe	missense_variant	Exon 1 of 2	1	NM_001099667.3	ENSP00000436682.1
ENSG00000285955	ENST00000647969.1	n.182+3523G>A		intron_variant	Intron 1 of 1
ENSG00000285955	ENST00000650300.1	n.1852+3523G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 15, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.245C>T (p.S82F) alteration is located in exon 1 (coding exon 1) of the ARMS2 gene. This alteration results from a C to T substitution at nucleotide position 245, causing the serine (S) at amino acid position 82 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	0.16
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.9
DANN	Benign	0.91
DEOGEN2	Benign	0.050	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0071	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.036
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.18	B
Vest4		0.13
MutPred		0.26		Loss of glycosylation at S82 (P = 0.0241);
MVP		0.014
MPC		1.3
ClinPred		0.15	T
GERP RS		-1.2
Varity_R		0.18
gMVP		0.014

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.

Other links and lift over

hg19: chr10-124214488;