Genetic Variant SULT1A2:p.Glu218Lys (chr16-28592386-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 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. 12/21 in silico tools predict a benign outcome for this variant. 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

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

Variant links:

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]

SULT1A2 links:

ENSG00000288656 (HGNC:):

ENSG00000288656 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 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
SULT1A2	NM_001054.4 link	c.652G>A	p.Glu218Lys	missense_variant	Exon 7 of 8	ENST00000335715.9	NP_001045.2	P50226

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT1A2	ENST00000335715.9 link	c.652G>A	p.Glu218Lys	missense_variant	Exon 7 of 8	1	NM_001054.4	ENSP00000338742.4		P50226

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1460362

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726514

show subpopulations

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:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.652G>A (p.E218K) alteration is located in exon 7 (coding exon 6) of the SULT1A2 gene. This alteration results from a G to A substitution at nucleotide position 652, causing the glutamic acid (E) at amino acid position 218 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.32

CADD

Benign

7.5

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

T;T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.78

T;.;T

M_CAP

Benign

0.0088

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.6

.;M;M

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.7

N;N;N

REVEL

Uncertain

0.38

Sift

Uncertain

0.0080

D;T;T

Sift4G

Benign

0.15

T;T;T

Polyphen

0.80

.;P;P

Vest4

0.22

MutPred

0.70

.;Gain of ubiquitination at E218 (P = 0.0128);Gain of ubiquitination at E218 (P = 0.0128);

MVP

0.86

MPC

0.081

ClinPred

0.46

GERP RS

1.9

Varity_R

0.32

gMVP

0.41

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over