chr19-48591631-C-T
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2PP3_StrongPP5_Moderate
The NM_177973.2(SULT2B1):c.446C>T(p.Pro149Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Consequence
SULT2B1
NM_177973.2 missense
NM_177973.2 missense
Scores
7
8
4
Clinical Significance
Conservation
PhyloP100: 5.69
Genes affected
SULT2B1 (HGNC:11459): (sulfotransferase family 2B 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 sulfates dehydroepiandrosterone but not 4-nitrophenol, a typical substrate for the phenol and estrogen sulfotransferase subfamilies. Two alternatively spliced variants that encode different isoforms have been described. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.976
PP5
Variant 19-48591631-C-T is Pathogenic according to our data. Variant chr19-48591631-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 426107.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SULT2B1 | NM_177973.2 | c.446C>T | p.Pro149Leu | missense_variant | 4/7 | ENST00000201586.7 | |
SULT2B1 | NM_004605.2 | c.401C>T | p.Pro134Leu | missense_variant | 3/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SULT2B1 | ENST00000201586.7 | c.446C>T | p.Pro149Leu | missense_variant | 4/7 | 1 | NM_177973.2 | P2 | |
SULT2B1 | ENST00000323090.4 | c.401C>T | p.Pro134Leu | missense_variant | 3/6 | 1 | A2 | ||
ENST00000666424.1 | n.493+5115G>A | intron_variant, non_coding_transcript_variant | |||||||
SULT2B1 | ENST00000594274.1 | n.196C>T | non_coding_transcript_exon_variant | 2/5 | 3 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 31
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive congenital ichthyosis 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | research | Institute for Human Genetics, University Medical Center Freiburg | Jul 01, 2016 | 15- and 11-year-old Tunisian males (siblings) with autosomal recessive congenital ichthyosis manifesting as lamellar ichthyosis (ARCI1; 1242300) presented the homozygous missense mutation Pro149Leu in SULT2B1. The ichthyosis showed sparing of several body regions such as the popliteal fossa, axilla, back and part of the soles, similar to individuals with X-linked ichthyosis (XLI; 308100). - |
Ichthyosis, congenital, autosomal recessive 14 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 13, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Gain of MoRF binding (P = 0.032);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at