NM_177973.2:c.320T>C

Variant names:

• chr19-48587334-T-C
• rs1973577056
• NM_177973.2:c.320T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_177973.2(SULT2B1):​c.320T>C​(p.Ile107Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SULT2B1 NM_177973.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.812
• Publications: 0 publications found

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: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287603 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06575391).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177973.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT2B1	NM_177973.2	MANE Select	c.320T>C	p.Ile107Thr	missense	Exon 3 of 7	NP_814444.1	O00204-1
	SULT2B1	NM_004605.2		c.275T>C	p.Ile92Thr	missense	Exon 2 of 6	NP_004596.2	O00204-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT2B1	ENST00000201586.7	TSL:1 MANE Select	c.320T>C	p.Ile107Thr	missense	Exon 3 of 7	ENSP00000201586.2	O00204-1
	SULT2B1	ENST00000323090.4	TSL:1	c.275T>C	p.Ile92Thr	missense	Exon 2 of 6	ENSP00000312880.3	O00204-2
	ENSG00000287603	ENST00000666424.1		n.493+9412A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461868 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	15
DANN	Benign	0.35
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.81
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.31	N
REVEL	Benign	0.19
Sift	Benign	0.61	T
Sift4G	Benign	0.58	T
Polyphen		0.0010	B
Vest4		0.23
MutPred		0.51		Loss of sheet (P = 0.0817)
MVP		0.17
MPC		0.36
ClinPred		0.039	T
GERP RS		2.7
Varity_R		0.31
gMVP		0.57
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1973577056; hg19: chr19-49090591;