chr16-28593254-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001054.4(SULT1A2):​c.592G>A​(p.Glu198Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E198V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SULT1A2
NM_001054.4 missense, splice_region

Scores

2
17
Splicing: ADA: 0.002077
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66
Variant links:
Genes affected
SULT1A2 (HGNC:11454): (sulfotransferase family 1A member 2) Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members. This gene encodes one of two phenol sulfotransferases with thermostable enzyme activity. Two alternatively spliced variants that encode the same protein have been described. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17880103).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SULT1A2NM_001054.4 linkc.592G>A p.Glu198Lys missense_variant, splice_region_variant Exon 6 of 8 ENST00000335715.9 NP_001045.2 P50226

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SULT1A2ENST00000335715.9 linkc.592G>A p.Glu198Lys missense_variant, splice_region_variant Exon 6 of 8 1 NM_001054.4 ENSP00000338742.4 P50226

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
251024
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135600
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461250
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
726928
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
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
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 15, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.592G>A (p.E198K) alteration is located in exon 6 (coding exon 5) of the SULT1A2 gene. This alteration results from a G to A substitution at nucleotide position 592, causing the glutamic acid (E) at amino acid position 198 to be replaced by a lysine (K). 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
0.22
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
20
DANN
Uncertain
0.99
DEOGEN2
Benign
0.27
T;T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.26
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.80
.;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-0.66
T
MutationAssessor
Benign
0.41
N;N
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.9
N;N
REVEL
Benign
0.26
Sift
Benign
0.27
T;T
Sift4G
Benign
0.38
T;T
Polyphen
0.10
B;B
Vest4
0.42
MutPred
0.51
Gain of methylation at E198 (P = 0.0024);Gain of methylation at E198 (P = 0.0024);
MVP
0.77
MPC
0.090
ClinPred
0.20
T
GERP RS
2.3
Varity_R
0.38
gMVP
0.34

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0021
dbscSNV1_RF
Benign
0.022
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: rs778431880; hg19: chr16-28604575; API