chr19-47883590-C-A

Variant summary

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

The NM_003167.4(SULT2A1):​c.332G>T​(p.Ser111Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

SULT2A1
NM_003167.4 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.49
Variant links:
Genes affected
SULT2A1 (HGNC:11458): (sulfotransferase family 2A member 1) This gene encodes a member of the sulfotransferase family. Sulfotransferases aid in the metabolism of drugs and endogenous compounds by converting these substances into more hydrophilic water-soluble sulfate conjugates that can be easily excreted. This protein catalyzes the sulfation of steroids and bile acids in the liver and adrenal glands, and may have a role in the inherited adrenal androgen excess in women with polycystic ovary syndrome. [provided by RefSeq, Mar 2010]

Genome browser will be placed here

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=0.2830361).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SULT2A1NM_003167.4 linkuse as main transcriptc.332G>T p.Ser111Ile missense_variant 2/6 ENST00000222002.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SULT2A1ENST00000222002.4 linkuse as main transcriptc.332G>T p.Ser111Ile missense_variant 2/61 NM_003167.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152100
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461876
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727240
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:
0.00000989
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152100
Hom.:
0
Cov.:
30
AF XY:
0.0000135
AC XY:
1
AN XY:
74294
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000151

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 GeneticsJan 25, 2023The c.332G>T (p.S111I) alteration is located in exon 2 (coding exon 2) of the SULT2A1 gene. This alteration results from a G to T substitution at nucleotide position 332, causing the serine (S) at amino acid position 111 to be replaced by an isoleucine (I). 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
0.17
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
11
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.52
D
Eigen
Benign
-0.85
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.72
T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.28
T
MetaSVM
Uncertain
0.044
D
MutationAssessor
Uncertain
2.5
M
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.40
T
PROVEAN
Uncertain
-4.1
D
REVEL
Uncertain
0.38
Sift
Uncertain
0.0050
D
Sift4G
Uncertain
0.057
T
Polyphen
0.94
P
Vest4
0.17
MutPred
0.49
Gain of methylation at K113 (P = 0.0519);
MVP
0.66
MPC
0.47
ClinPred
0.96
D
GERP RS
-7.1
Varity_R
0.37
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs377270215; hg19: chr19-48386847; API