4-69730622-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014465.4(SULT1B1):ā€‹c.657G>Cā€‹(p.Glu219Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000837 in 1,613,122 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000072 ( 0 hom., cov: 32)
Exomes š‘“: 0.000085 ( 1 hom. )

Consequence

SULT1B1
NM_014465.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.62
Variant links:
Genes affected
SULT1B1 (HGNC:17845): (sulfotransferase family 1B 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. However, the total genomic length of this gene is greater than that of other SULT1 genes. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.011909038).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SULT1B1NM_014465.4 linkc.657G>C p.Glu219Asp missense_variant 7/8 ENST00000310613.8 NP_055280.2 O43704

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SULT1B1ENST00000310613.8 linkc.657G>C p.Glu219Asp missense_variant 7/81 NM_014465.4 ENSP00000308770.2 O43704

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000524
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:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000195
AC:
49
AN:
250808
Hom.:
0
AF XY:
0.000170
AC XY:
23
AN XY:
135584
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000988
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:
0.000491
GnomAD4 exome
AF:
0.0000849
AC:
124
AN:
1460956
Hom.:
1
Cov.:
31
AF XY:
0.0000784
AC XY:
57
AN XY:
726812
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00103
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:
0.0000666
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152166
Hom.:
0
Cov.:
32
AF XY:
0.0000942
AC XY:
7
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000524
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000647
Hom.:
0
Bravo
AF:
0.000110
ExAC
AF:
0.000214
AC:
26
Asia WGS
AF:
0.000289
AC:
1
AN:
3476
EpiCase
AF:
0.00
EpiControl
AF:
0.000178

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 GeneticsOct 16, 2024The c.657G>C (p.E219D) alteration is located in exon 7 (coding exon 6) of the SULT1B1 gene. This alteration results from a G to C substitution at nucleotide position 657, causing the glutamic acid (E) at amino acid position 219 to be replaced by an aspartic acid (D). 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
0.084
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
0.66
DANN
Benign
0.96
DEOGEN2
Benign
0.26
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.14
T
M_CAP
Benign
0.0056
T
MetaRNN
Benign
0.012
T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
1.2
L
PrimateAI
Benign
0.36
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.23
Sift
Benign
0.12
T
Sift4G
Benign
0.13
T
Polyphen
0.0
B
Vest4
0.10
MutPred
0.63
Loss of stability (P = 0.0895);
MVP
0.34
MPC
0.015
ClinPred
0.025
T
GERP RS
-7.0
Varity_R
0.15
gMVP
0.30

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: rs546925597; hg19: chr4-70596340; API