2-108247199-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001320878.2(SULT1C3):​c.5C>A​(p.Ala2Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000735 in 1,361,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

SULT1C3
NM_001320878.2 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.681

Publications

0 publications found
Variant links:
Genes affected
SULT1C3 (HGNC:33543): (sulfotransferase family 1C member 3) Enables 3'-phosphoadenosine 5'-phosphosulfate binding activity and sulfotransferase activity. Involved in 3'-phosphoadenosine 5'-phosphosulfate metabolic process; cholesterol metabolic process; and xenobiotic metabolic process. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11881399).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SULT1C3NM_001320878.2 linkc.5C>A p.Ala2Glu missense_variant Exon 2 of 8 ENST00000681802.2 NP_001307807.1 Q6IMI6-2
SULT1C3NM_001008743.3 linkc.5C>A p.Ala2Glu missense_variant Exon 2 of 8 NP_001008743.1 Q6IMI6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SULT1C3ENST00000681802.2 linkc.5C>A p.Ala2Glu missense_variant Exon 2 of 8 NM_001320878.2 ENSP00000505748.1 Q6IMI6-2
SULT1C3ENST00000329106.3 linkc.5C>A p.Ala2Glu missense_variant Exon 2 of 8 2 ENSP00000333310.2 Q6IMI6-1
ENSG00000294676ENST00000725207.1 linkn.168-11336G>T intron_variant Intron 1 of 1
ENSG00000294676ENST00000725208.1 linkn.43-11336G>T intron_variant Intron 1 of 1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.35e-7
AC:
1
AN:
1361314
Hom.:
0
Cov.:
32
AF XY:
0.00000149
AC XY:
1
AN XY:
670526
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
29748
American (AMR)
AF:
0.00
AC:
0
AN:
32570
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22796
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37258
South Asian (SAS)
AF:
0.00
AC:
0
AN:
68104
European-Finnish (FIN)
AF:
0.0000197
AC:
1
AN:
50664
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5384
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1059160
Other (OTH)
AF:
0.00
AC:
0
AN:
55630
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
8.9
DANN
Benign
0.87
DEOGEN2
Benign
0.0011
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.0046
N
LIST_S2
Benign
0.23
T
M_CAP
Benign
0.0018
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
0.0
N
PhyloP100
0.68
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.28
N
REVEL
Benign
0.034
Sift
Benign
0.042
D
Sift4G
Uncertain
0.057
T
Polyphen
0.049
B
Vest4
0.28
MutPred
0.27
Loss of ubiquitination at K3 (P = 0.0352);
MVP
0.10
MPC
0.39
ClinPred
0.30
T
GERP RS
0.80
Varity_R
0.076
gMVP
0.65
Mutation Taster
=99/1
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

Publications

Other links and lift over

dbSNP: rs758796049; hg19: chr2-108863655; API