chr19-48599256-C-G

Position:

• chr19-48599256-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_177973.2(SULT2B1):​c.948C>G​(p.Asp316Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,668 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SULT2B1 NM_177973.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343

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 (HGNC:):

ACMG classification

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=0.063382775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULT2B1	NM_177973.2	c.948C>G	p.Asp316Glu	missense_variant	7/7	ENST00000201586.7	NP_814444.1
SULT2B1	NM_004605.2	c.903C>G	p.Asp301Glu	missense_variant	6/6		NP_004596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULT2B1	ENST00000201586.7	c.948C>G	p.Asp316Glu	missense_variant	7/7	1	NM_177973.2	ENSP00000201586.2
SULT2B1	ENST00000323090.4	c.903C>G	p.Asp301Glu	missense_variant	6/6	1		ENSP00000312880.3
SULT2B1	ENST00000594274.1	n.698C>G		non_coding_transcript_exon_variant	5/5	3
SULT2B1	ENST00000597923.1	n.1256C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000418 AC: 1 AN: 239312 Hom.: 0 AF XY: 0.00000768 AC XY: 1 AN XY: 130242

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000931

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457668 Hom.: 0 Cov.: 36 AF XY: 0.00000138 AC XY: 1 AN XY: 724846

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.10
DANN	Uncertain	0.98
DEOGEN2	Benign	0.088	T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.29	T;T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.063	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.37	N;N
REVEL	Benign	0.042
Sift	Benign	0.031	D;D
Sift4G	Uncertain	0.040	D;D
Polyphen		0.067	B;B
Vest4		0.21
MutPred		0.15		Gain of glycosylation at P313 (P = 0.1402);.;
MVP		0.23
MPC		0.26
ClinPred		0.061	T
GERP RS		-2.2
Varity_R		0.056
gMVP		0.039

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: rs1052131; hg19: chr19-49102513;