19-48591631-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM2 PP3_Strong PP5_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
• Clinical Significance: Pathogenic criteria provided, single submitter P:2
• 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]

(HGNC:):

ACMG classification

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

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

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: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.066	T
BayesDel_noAF	Benign	-0.14
Cadd	Pathogenic	27
Dann	Pathogenic	1.0
DEOGEN2	Uncertain	0.79	D;.
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.032	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Pathogenic	4.3	H;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.59	T
PROVEAN	Pathogenic	-9.8	D;D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;D
Vest4		0.95
MutPred		0.86		Gain of MoRF binding (P = 0.032);.;
MVP		0.36
MPC		0.98
ClinPred		1.0	D
GERP RS		4.5
Varity_R		0.95
gMVP		0.89

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

Other links and lift over

dbSNP: rs1114167424; hg19: chr19-49094888;