chr19-47882102-A-G

Variant names:

• chr19-47882102-A-G
• rs139437036
• NM_003167.4:c.454T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003167.4(SULT2A1):​c.454T>C​(p.Trp152Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,554 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. W152G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SULT2A1 NM_003167.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127
• Publications: 0 publications found

Genes affected

SULT2A1 (HGNC:11458): (sulfotransferase family 2A member 1) This gene encodes a member of the sulfotransferase family. Sulfotransferases aid in the metabolism of drugs and endogenous compounds by converting these substances into more hydrophilic water-soluble sulfate conjugates that can be easily excreted. This protein catalyzes the sulfation of steroids and bile acids in the liver and adrenal glands, and may have a role in the inherited adrenal androgen excess in women with polycystic ovary syndrome. [provided by RefSeq, Mar 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT2A1	NM_003167.4	c.454T>C	p.Trp152Arg	missense_variant	Exon 3 of 6	ENST00000222002.4	NP_003158.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT2A1	ENST00000222002.4	c.454T>C	p.Trp152Arg	missense_variant	Exon 3 of 6	1	NM_003167.4	ENSP00000222002.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461554 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727050

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86162

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111892

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	16
DANN	Benign	0.66
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.13
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Uncertain	0.35
Sift	Benign	0.54	T
Sift4G	Benign	0.56	T
Polyphen		0.87	P
Vest4		0.44
MutPred		0.48		Gain of catalytic residue at W152 (P = 0.0329);
MVP		0.75
MPC		0.38
ClinPred		0.29	T
GERP RS		1.9
Varity_R		0.52
gMVP		0.47
Mutation Taster		=81/19	polymorphism

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

Other links and lift over

dbSNP: rs139437036; hg19: chr19-48385359;