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GeneBe

21-45180351-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_001112.4(ADARB1):​c.985C>T​(p.Arg329Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ADARB1
NM_001112.4 missense

Scores

2
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.78
Variant links:
Genes affected
ADARB1 (HGNC:226): (adenosine deaminase RNA specific B1) This gene encodes the enzyme responsible for pre-mRNA editing of the glutamate receptor subunit B by site-specific deamination of adenosines. Studies in rat found that this enzyme acted on its own pre-mRNA molecules to convert an AA dinucleotide to an AI dinucleotide which resulted in a new splice site. Alternative splicing of this gene results in several transcript variants, some of which have been characterized by the presence or absence of an ALU cassette insert and a short or long C-terminal region. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, ADARB1

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADARB1NM_001112.4 linkuse as main transcriptc.985C>T p.Arg329Cys missense_variant 5/11 ENST00000348831.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADARB1ENST00000348831.9 linkuse as main transcriptc.985C>T p.Arg329Cys missense_variant 5/111 NM_001112.4 P1P78563-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461786
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727192
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 16, 2022The c.985C>T (p.R329C) alteration is located in exon 5 (coding exon 3) of the ADARB1 gene. This alteration results from a C to T substitution at nucleotide position 985, causing the arginine (R) at amino acid position 329 to be replaced by a cysteine (C). 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
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.78
D;.;.;.;D
Eigen
Uncertain
0.67
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.93
D;D;D;D;.
M_CAP
Benign
0.049
D
MetaRNN
Uncertain
0.61
D;D;D;D;D
MetaSVM
Benign
-0.80
T
MutationAssessor
Uncertain
2.2
M;M;M;.;M
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.64
T
Sift4G
Uncertain
0.0070
D;D;D;D;D
Polyphen
1.0
D;D;.;.;D
Vest4
0.64
MutPred
0.53
Gain of catalytic residue at L330 (P = 0.0107);Gain of catalytic residue at L330 (P = 0.0107);Gain of catalytic residue at L330 (P = 0.0107);.;Gain of catalytic residue at L330 (P = 0.0107);
MVP
0.53
ClinPred
1.0
D
GERP RS
5.4
Varity_R
0.62
gMVP
0.65

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: chr21-46600266; API