Genetic Variant SULT1A2:p.Ile7Thr (chr16-28595911-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001054.4(SULT1A2):c.20T>C(p.Ile7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,273,122 control chromosomes in the GnomAD database, including 90,374 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 7959 hom., cov: 29)

Exomes 𝑓: 0.24 ( 82415 hom. )

Consequence

SULT1A2
NM_001054.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.667

Publications

29 publications found

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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0042673945).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1A2	NM_001054.4 link	c.20T>C	p.Ile7Thr	missense_variant	Exon 2 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.20T>C	p.Ile7Thr	missense_variant	Exon 2 of 8	1	NM_001054.4	ENSP00000338742.4		P50226

Frequencies

GnomAD3 genomes

AF:

0.310

AC:

46667

AN:

150586

Hom.:

7947

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.168

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.272

Gnomad EAS

AF:

0.0696

Gnomad SAS

AF:

0.180

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.284

GnomAD2 exomes

AF:

0.0773

AC:

13567

AN:

175472

AF XY:

0.0709

show subpopulations

Gnomad AFR exome

AF:

0.0366

Gnomad AMR exome

AF:

0.176

Gnomad ASJ exome

AF:

0.0704

Gnomad EAS exome

AF:

0.00644

Gnomad FIN exome

AF:

0.0960

Gnomad NFE exome

AF:

0.0785

Gnomad OTH exome

AF:

0.0914

GnomAD4 exome

AF:

0.237

AC:

266492

AN:

1122416

Hom.:

82415

Cov.:

AF XY:

0.233

AC XY:

131687

AN XY:

564316

show subpopulations

African (AFR)

AF:

0.145

AC:

4146

AN:

28514

American (AMR)

AF:

0.295

AC:

10781

AN:

36488

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

4546

AN:

22786

East Asian (EAS)

AF:

0.0853

AC:

3323

AN:

38968

South Asian (SAS)

AF:

0.137

AC:

10685

AN:

77876

European-Finnish (FIN)

AF:

0.388

AC:

16903

AN:

43532

Middle Eastern (MID)

AF:

0.133

AC:

482

AN:

3618

European-Non Finnish (NFE)

AF:

0.249

AC:

204251

AN:

820962

Other (OTH)

AF:

0.229

AC:

11375

AN:

49672

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

6410

12821

19231

25642

32052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3170

6340

9510

12680

15850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.310

AC:

46716

AN:

150706

Hom.:

7959

Cov.:

AF XY:

0.309

AC XY:

22700

AN XY:

73554

show subpopulations

African (AFR)

AF:

0.232

AC:

9534

AN:

41152

American (AMR)

AF:

0.332

AC:

5040

AN:

15160

Ashkenazi Jewish (ASJ)

AF:

0.272

AC:

933

AN:

3434

East Asian (EAS)

AF:

0.0698

AC:

358

AN:

5130

South Asian (SAS)

AF:

0.180

AC:

860

AN:

4768

European-Finnish (FIN)

AF:

0.446

AC:

4638

AN:

10404

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.364

AC:

24556

AN:

67370

Other (OTH)

AF:

0.281

AC:

587

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

1466

2931

4397

5862

7328

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.243

Hom.:

1100

Bravo

AF:

0.304

ExAC

AF:

0.137

AC:

16356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0020

(source)

DANN

Benign

0.20

DEOGEN2

Benign

0.0086

T;T;T;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.0034

T;.;T;T

MetaRNN

Benign

0.0043

T;T;T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.77

.;N;N;.

PhyloP100

-0.67

PrimateAI

Benign

0.40

PROVEAN

Benign

0.67

N;N;N;N

REVEL

Benign

0.013

Sift

Benign

0.63

T;T;T;T

Sift4G

Benign

0.49

T;T;T;T

Polyphen

0.0

.;B;B;.

Vest4

0.013

MPC

0.088

ClinPred

0.00021

GERP RS

-4.5

PromoterAI

-0.012

Neutral

(source)

Varity_R

0.026

gMVP

0.62

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over