rs1114167424

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong

The NM_177973.2(SULT2B1):c.446C>A(p.Pro149His) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P149L) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SULT2B1
NM_177973.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.69

Publications

0 publications found

Variant links:

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]

SULT2B1 Gene-Disease associations (from GenCC):

ichthyosis, congenital, autosomal recessive 14
Inheritance: AR Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
lamellar ichthyosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SULT2B1 links:

ENSG00000287603 (HGNC:):

ENSG00000287603 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr19-48591631-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 426107.Status of the report is criteria_provided_single_submitter, 1 stars.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.972

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT2B1	NM_177973.2 link	c.446C>A	p.Pro149His	missense_variant	Exon 4 of 7	ENST00000201586.7	NP_814444.1	O00204-1
SULT2B1	NM_004605.2 link	c.401C>A	p.Pro134His	missense_variant	Exon 3 of 6		NP_004596.2	O00204-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SULT2B1	ENST00000201586.7 link	c.446C>A	p.Pro149His	missense_variant	Exon 4 of 7	1	NM_177973.2	ENSP00000201586.2	O00204-1
SULT2B1	ENST00000323090.4 link	c.401C>A	p.Pro134His	missense_variant	Exon 3 of 6	1		ENSP00000312880.3	O00204-2
SULT2B1	ENST00000594274.1 link	n.196C>A		non_coding_transcript_exon_variant	Exon 2 of 5	3
ENSG00000287603	ENST00000666424.1 link	n.493+5115G>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461282

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726942

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86240

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111606

Other (OTH)

AF:

0.00

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.84

D;.

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.018

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Benign

-0.59

MutationAssessor

Pathogenic

4.3

H;.

PhyloP100

5.7

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-8.9

D;D

REVEL

Uncertain

0.30

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.93

MutPred

0.85

Gain of MoRF binding (P = 0.0629);.;

MVP

0.37

MPC

1.0

ClinPred

1.0

GERP RS

4.5

Varity_R

0.98

gMVP

0.87

Mutation Taster

=20/80

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over