16-28592047-C-T

Variant names:

• chr16-28592047-C-T
• rs1234468149
• NM_001054.4:c.869G>A

Variant summary

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

The NM_001054.4(SULT1A2):​c.869G>A​(p.Ser290Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,459,534 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: 33)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: SULT1A2 NM_001054.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.89
• Publications: 0 publications found

Genes affected

SULT1A2 (HGNC:11454): (sulfotransferase family 1A member 2) 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 encodes one of two phenol sulfotransferases with thermostable enzyme activity. Two alternatively spliced variants that encode the same protein have been described. [provided by RefSeq, Jul 2008]

ENSG00000289754 (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=0.042380333).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001054.4. 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
	SULT1A2	NM_001054.4	MANE Select	c.869G>A	p.Ser290Asn	missense	Exon 8 of 8	NP_001045.2	P50226
	SULT1A2	NM_001400258.1		c.869G>A	p.Ser290Asn	missense	Exon 9 of 9	NP_001387187.1	P50226
	SULT1A2	NM_001400259.1		c.869G>A	p.Ser290Asn	missense	Exon 9 of 9	NP_001387188.1	P50226

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1A2	ENST00000335715.9	TSL:1 MANE Select	c.869G>A	p.Ser290Asn	missense	Exon 8 of 8	ENSP00000338742.4	P50226
	SULT1A2	ENST00000898358.1		c.1019G>A	p.Ser340Asn	missense	Exon 7 of 7	ENSP00000568417.1
	SULT1A2	ENST00000898343.1		c.884G>A	p.Ser295Asn	missense	Exon 8 of 8	ENSP00000568402.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000280 AC: 7 AN: 250300 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000548 AC: 8 AN: 1459534 Hom.: 0 Cov.: 41 AF XY: 0.00000413 AC XY: 3 AN XY: 726052

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.000179 AC: 8 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4142

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111822

Other (OTH) AF: 0.00 AC: 0 AN: 60210

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.14
DANN	Benign	0.86
DEOGEN2	Benign	0.0092	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0051	N
LIST_S2	Benign	0.21	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.59	N
PhyloP100		-1.9
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.050	N
REVEL	Benign	0.030
Sift	Benign	0.31	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.24		Loss of phosphorylation at S290 (P = 0.0644)
MVP		0.081
MPC		1.3
ClinPred		0.050	T
GERP RS		-2.7
Varity_R		0.055
gMVP		0.26

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: rs1234468149; hg19: chr16-28603368;