6-131583831-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_000045.4(ARG1):​c.892G>T​(p.Ala298Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,812 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. 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

ARG1
NM_000045.4 missense

Scores

1
2
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.78
Variant links:
Genes affected
ARG1 (HGNC:663): (arginase 1) Arginase catalyzes the hydrolysis of arginine to ornithine and urea. At least two isoforms of mammalian arginase exist (types I and II) which differ in their tissue distribution, subcellular localization, immunologic crossreactivity and physiologic function. The type I isoform encoded by this gene, is a cytosolic enzyme and expressed predominantly in the liver as a component of the urea cycle. Inherited deficiency of this enzyme results in argininemia, an autosomal recessive disorder characterized by hyperammonemia. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
MED23 (HGNC:2372): (mediator complex subunit 23) The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. This protein also acts as a metastasis suppressor. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2012]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36465874).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ARG1NM_000045.4 linkc.892G>T p.Ala298Ser missense_variant Exon 8 of 8 ENST00000368087.8 NP_000036.2 P05089-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ARG1ENST00000368087.8 linkc.892G>T p.Ala298Ser missense_variant Exon 8 of 8 1 NM_000045.4 ENSP00000357066.3 P05089-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461812
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727204
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.091
BayesDel_addAF
Uncertain
0.043
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.34
T;.;.
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.14
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.81
T;T;T
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.36
T;T;T
MetaSVM
Benign
-0.73
T
MutationAssessor
Benign
0.36
N;.;.
PrimateAI
Benign
0.41
T
PROVEAN
Benign
1.8
N;N;.
REVEL
Benign
0.26
Sift
Benign
0.68
T;T;.
Sift4G
Benign
0.88
T;T;.
Polyphen
0.011
B;B;.
Vest4
0.084
MutPred
0.54
Loss of glycosylation at T295 (P = 0.1732);.;.;
MVP
0.85
MPC
0.058
ClinPred
0.77
D
GERP RS
5.1
Varity_R
0.33
gMVP
0.46

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: chr6-131904971; COSMIC: COSV51581586; COSMIC: COSV51581586; API