NM_001099667.3:c.245C>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 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
• Publications: 0 publications found

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]

HTRA1-AS1 (HGNC:58122):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06571522).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001099667.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMS2	NM_001099667.3	MANE Select	c.245C>T	p.Ser82Phe	missense	Exon 1 of 2	NP_001093137.1	P0C7Q2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ARMS2	ENST00000528446.1	TSL:1 MANE Select	c.245C>T	p.Ser82Phe	missense	Exon 1 of 2	ENSP00000436682.1	P0C7Q2
	HTRA1-AS1	ENST00000647969.1		n.182+3523G>A		intron	N/A
	HTRA1-AS1	ENST00000650300.1		n.1852+3523G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-1.6
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
PromoterAI		0.018	Neutral
Varity_R		0.18
gMVP		0.014
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr10-124214488;