chr2-108247349-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001320878.2(SULT1C3):​c.155C>A​(p.Ala52Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,394,128 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SULT1C3
NM_001320878.2 missense

Scores

5
7
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.632
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 made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.916

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SULT1C3NM_001320878.2 linkc.155C>A p.Ala52Glu missense_variant Exon 2 of 8 ENST00000681802.2 NP_001307807.1 Q6IMI6-2
SULT1C3NM_001008743.3 linkc.155C>A p.Ala52Glu 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.155C>A p.Ala52Glu missense_variant Exon 2 of 8 NM_001320878.2 ENSP00000505748.1 Q6IMI6-2
SULT1C3ENST00000329106.3 linkc.155C>A p.Ala52Glu missense_variant Exon 2 of 8 2 ENSP00000333310.2 Q6IMI6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000143
AC:
2
AN:
1394128
Hom.:
0
Cov.:
33
AF XY:
0.00000145
AC XY:
1
AN XY:
690322
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000264
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.28e-7
Gnomad4 OTH exome
AF:
0.00
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
Aug 14, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.155C>A (p.A52E) alteration is located in exon 1 (coding exon 1) of the SULT1C3 gene. This alteration results from a C to A substitution at nucleotide position 155, causing the alanine (A) at amino acid position 52 to be replaced by a glutamic acid (E). 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
Pathogenic
0.82
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.14
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Uncertain
0.45
T
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.058
N
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.019
T
MetaRNN
Pathogenic
0.92
D
MetaSVM
Uncertain
-0.060
T
MutationAssessor
Pathogenic
4.0
H
PrimateAI
Benign
0.43
T
PROVEAN
Uncertain
-3.7
D
REVEL
Uncertain
0.53
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0040
D
Polyphen
0.99
D
Vest4
0.69
MutPred
0.76
Gain of ubiquitination at K56 (P = 0.0719);
MVP
0.54
MPC
0.36
ClinPred
0.74
D
GERP RS
2.4
Varity_R
0.88
gMVP
0.83

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: chr2-108863805; COSMIC: COSV61252682; API