chr19-48576052-C-A

Variant names:

• chr19-48576052-C-A
• rs931741083
• NM_177973.2:c.183C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_177973.2(SULT2B1):​c.183C>A​(p.Asp61Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SULT2B1 NM_177973.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.00

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]

ENSG00000287603 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1778652).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT2B1	NM_177973.2	c.183C>A	p.Asp61Glu	missense_variant	Exon 2 of 7	ENST00000201586.7	NP_814444.1
SULT2B1	NM_004605.2	c.138C>A	p.Asp46Glu	missense_variant	Exon 1 of 6		NP_004596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT2B1	ENST00000201586.7	c.183C>A	p.Asp61Glu	missense_variant	Exon 2 of 7	1	NM_177973.2	ENSP00000201586.2
SULT2B1	ENST00000323090.4	c.138C>A	p.Asp46Glu	missense_variant	Exon 1 of 6	1		ENSP00000312880.3
ENSG00000287603	ENST00000666424.1	n.493+20694G>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461106 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 726832

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Nov 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.183C>A (p.D61E) alteration is located in exon 2 (coding exon 2) of the SULT2B1 gene. This alteration results from a C to A substitution at nucleotide position 183, causing the aspartic acid (D) at amino acid position 61 to be replaced by a glutamic acid (E). 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	0.18
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.0
DANN	Benign	0.90
DEOGEN2	Uncertain	0.43	T;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.55	T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.54	N;N
REVEL	Benign	0.15
Sift	Benign	0.36	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.073	B;P
Vest4		0.20
MutPred		0.68		Loss of sheet (P = 0.1501);.;
MVP		0.13
MPC		0.31
ClinPred		0.49	T
GERP RS		1.0
Varity_R		0.18
gMVP		0.78

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: rs931741083; hg19: chr19-49079309;