4-69857541-G-C

Variant summary

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

The NM_005420.3(SULT1E1):ā€‹c.104C>Gā€‹(p.Ala35Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,612,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000046 ( 0 hom., cov: 32)
Exomes š‘“: 0.00014 ( 0 hom. )

Consequence

SULT1E1
NM_005420.3 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.67
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=0.31656283).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SULT1E1NM_005420.3 linkuse as main transcriptc.104C>G p.Ala35Gly missense_variant 2/8 ENST00000226444.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SULT1E1ENST00000226444.4 linkuse as main transcriptc.104C>G p.Ala35Gly missense_variant 2/81 NM_005420.3 P1
SULT1E1ENST00000504002.1 linkuse as main transcriptn.210C>G non_coding_transcript_exon_variant 2/51

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152080
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:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000599
AC:
15
AN:
250288
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135310
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000584
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000106
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.000138
AC:
201
AN:
1460780
Hom.:
0
Cov.:
31
AF XY:
0.000121
AC XY:
88
AN XY:
726682
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000450
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:
0.000176
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152080
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74292
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:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000254
Hom.:
0
Bravo
AF:
0.0000567
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000824
AC:
10

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 GeneticsAug 02, 2021The c.104C>G (p.A35G) alteration is located in exon 2 (coding exon 1) of the SULT1E1 gene. This alteration results from a C to G substitution at nucleotide position 104, causing the alanine (A) at amino acid position 35 to be replaced by a glycine (G). 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
0.28
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.44
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.73
D
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.35
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Uncertain
0.95
D
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.32
T
MetaSVM
Benign
-0.71
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-3.1
D
REVEL
Benign
0.19
Sift
Uncertain
0.0010
D
Sift4G
Uncertain
0.0070
D
Polyphen
0.94
P
Vest4
0.38
MVP
0.33
MPC
0.52
ClinPred
0.40
T
GERP RS
4.1
Varity_R
0.86
gMVP
0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150180382; hg19: chr4-70723259; API