chr4-69849527-C-T

Variant summary

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

The NM_005420.3(SULT1E1):​c.406G>A​(p.Val136Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,609,810 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V136A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SULT1E1
NM_005420.3 missense

Scores

10
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.90
Variant links:
Genes affected
SULT1E1 (HGNC:11377): (sulfotransferase family 1E member 1) 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 a protein that transfers a sulfo moiety to and from estrone, which may control levels of estrogen receptors. [provided by RefSeq, Jul 2008]

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=0.37331915).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SULT1E1NM_005420.3 linkc.406G>A p.Val136Ile missense_variant Exon 5 of 8 ENST00000226444.4 NP_005411.1 P49888Q53X91

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SULT1E1ENST00000226444.4 linkc.406G>A p.Val136Ile missense_variant Exon 5 of 8 1 NM_005420.3 ENSP00000226444.3 P49888
SULT1E1ENST00000504002.1 linkn.512G>A non_coding_transcript_exon_variant Exon 5 of 5 1

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
151982
Hom.:
0
Cov.:
32
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:
0.000769
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.0000442
AC:
11
AN:
249032
Hom.:
0
AF XY:
0.0000594
AC XY:
8
AN XY:
134648
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000494
Gnomad SAS exome
AF:
0.0000331
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000158
AC:
23
AN:
1457710
Hom.:
0
Cov.:
30
AF XY:
0.0000193
AC XY:
14
AN XY:
725196
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000480
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.01e-7
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152100
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74362
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000771
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000474
Bravo
AF:
0.0000113
ExAC
AF:
0.0000330
AC:
4

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 10, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.406G>A (p.V136I) alteration is located in exon 5 (coding exon 4) of the SULT1E1 gene. This alteration results from a G to A substitution at nucleotide position 406, causing the valine (V) at amino acid position 136 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
0.18
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.14
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.46
T
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.94
D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.37
T
MetaSVM
Uncertain
0.34
D
MutationAssessor
Uncertain
2.6
M
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.85
N
REVEL
Uncertain
0.58
Sift
Uncertain
0.022
D
Sift4G
Benign
0.063
T
Polyphen
0.51
P
Vest4
0.16
MutPred
0.84
Gain of ubiquitination at K132 (P = 0.1245);
MVP
0.72
MPC
0.12
ClinPred
0.25
T
GERP RS
3.8
Varity_R
0.21
gMVP
0.60

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs757405253; hg19: chr4-70715245; COSMIC: COSV105051130; COSMIC: COSV105051130; API