3-121586499-A-C

Variant summary

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

The NM_001012659.2(ARGFX):​c.847A>C​(p.Thr283Pro) 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. 14/20 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

ARGFX
NM_001012659.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0150
Variant links:
Genes affected
ARGFX (HGNC:30146): (arginine-fifty homeobox) Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This gene is a member of the ARGFX homeobox gene family. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=0.18907502).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ARGFXNM_001012659.2 linkuse as main transcriptc.847A>C p.Thr283Pro missense_variant 5/5 ENST00000334384.5 NP_001012677.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ARGFXENST00000334384.5 linkuse as main transcriptc.847A>C p.Thr283Pro missense_variant 5/53 NM_001012659.2 ENSP00000335578 P1
ARGFXENST00000651603.1 linkuse as main transcriptc.847A>C p.Thr283Pro missense_variant 4/4 ENSP00000498601 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMay 16, 2023The c.847A>C (p.T283P) alteration is located in exon 5 (coding exon 4) of the ARGFX gene. This alteration results from a A to C substitution at nucleotide position 847, causing the threonine (T) at amino acid position 283 to be replaced by a proline (P). 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
0.092
BayesDel_addAF
Uncertain
0.024
T
BayesDel_noAF
Benign
-0.20
CADD
Benign
17
DANN
Benign
0.78
DEOGEN2
Benign
0.0045
T
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.96
FATHMM_MKL
Benign
0.022
N
LIST_S2
Benign
0.32
T
M_CAP
Benign
0.049
D
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-0.40
T
MutationAssessor
Benign
1.7
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.2
N
REVEL
Uncertain
0.32
Sift
Uncertain
0.0020
D
Sift4G
Benign
0.18
T
Polyphen
0.99
D
Vest4
0.21
MutPred
0.42
Gain of disorder (P = 0.072);
MVP
0.34
MPC
0.46
ClinPred
0.48
T
GERP RS
-0.74
Varity_R
0.19

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.

Other links and lift over

dbSNP: rs1576445849; hg19: chr3-121305346; API