chr16-28592386-C-T

Variant names:

• chr16-28592386-C-T
• NM_001054.4:c.652G>A

Variant summary

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

The NM_001054.4(SULT1A2):​c.652G>A​(p.Glu218Lys) 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 1,460,362 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: SULT1A2 NM_001054.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.23
• 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]

ENSG00000288656 (HGNC:):

ACMG classification

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

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

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.652G>A	p.Glu218Lys	missense	Exon 7 of 8	NP_001045.2	P50226
	SULT1A2	NM_001400258.1		c.652G>A	p.Glu218Lys	missense	Exon 8 of 9	NP_001387187.1	P50226
	SULT1A2	NM_001400259.1		c.652G>A	p.Glu218Lys	missense	Exon 8 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.652G>A	p.Glu218Lys	missense	Exon 7 of 8	ENSP00000338742.4	P50226
	SULT1A2	ENST00000898358.1		c.802G>A	p.Glu268Lys	missense	Exon 6 of 7	ENSP00000568417.1
	SULT1A2	ENST00000898343.1		c.667G>A	p.Glu223Lys	missense	Exon 7 of 8	ENSP00000568402.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460362 Hom.: 0 Cov.: 41 AF XY: 0.00000688 AC XY: 5 AN XY: 726514

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53094

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1110900

Other (OTH) AF: 0.00 AC: 0 AN: 60332

GnomAD4 genome Cov.: 32

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	0.086
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	7.5
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0088	T
MetaRNN	Uncertain	0.71	D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		1.2
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.7	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.15	T
Polyphen		0.80	P
Vest4		0.22
MutPred		0.70		Gain of ubiquitination at E218 (P = 0.0128)
MVP		0.86
MPC		0.081
ClinPred		0.46	T
GERP RS		1.9
Varity_R		0.32
gMVP		0.41
Mutation Taster		=90/10	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

hg19: chr16-28603707;