Genetic Variant SULT1A2:p.Asn235Thr (chr16-28592334-T-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.704A>C(p.Asn235Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.343 in 1,613,462 control chromosomes in the GnomAD database, including 99,598 homozygotes. In-silico tool predicts 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 ( 8213 hom., cov: 32)

Exomes 𝑓: 0.35 ( 91385 hom. )

Consequence

SULT1A2
NM_001054.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.93

Publications

55 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0042153).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1A2	NM_001054.4 link	c.704A>C	p.Asn235Thr	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.704A>C	p.Asn235Thr	missense_variant	Exon 7 of 8	1	NM_001054.4	ENSP00000338742.4		P50226

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47408

AN:

151732

Hom.:

8202

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.169

Gnomad AMR

AF:

0.334

Gnomad ASJ

AF:

0.276

Gnomad EAS

AF:

0.0694

Gnomad SAS

AF:

0.186

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.368

Gnomad OTH

AF:

0.286

GnomAD2 exomes

AF:

0.317

AC:

79581

AN:

251216

AF XY:

0.311

show subpopulations

Gnomad AFR exome

AF:

0.236

Gnomad AMR exome

AF:

0.384

Gnomad ASJ exome

AF:

0.278

Gnomad EAS exome

AF:

0.0623

Gnomad FIN exome

AF:

0.445

Gnomad NFE exome

AF:

0.361

Gnomad OTH exome

AF:

0.325

GnomAD4 exome

AF:

0.346

AC:

506055

AN:

1461612

Hom.:

91385

Cov.:

105

AF XY:

0.342

AC XY:

248904

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.227

AC:

7581

AN:

33464

American (AMR)

AF:

0.389

AC:

17413

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.273

AC:

7138

AN:

26132

East Asian (EAS)

AF:

0.0993

AC:

3941

AN:

39696

South Asian (SAS)

AF:

0.196

AC:

16897

AN:

86244

European-Finnish (FIN)

AF:

0.442

AC:

23618

AN:

53416

Middle Eastern (MID)

AF:

0.201

AC:

1156

AN:

5762

European-Non Finnish (NFE)

AF:

0.368

AC:

409257

AN:

1111808

Other (OTH)

AF:

0.316

AC:

19054

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

26590

53180

79771

106361

132951

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12674

25348

38022

50696

63370

<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:

0.313

AC:

47454

AN:

151850

Hom.:

8213

Cov.:

AF XY:

0.312

AC XY:

23129

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.232

AC:

9592

AN:

41414

American (AMR)

AF:

0.336

AC:

5117

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.276

AC:

957

AN:

3464

East Asian (EAS)

AF:

0.0696

AC:

356

AN:

5116

South Asian (SAS)

AF:

0.185

AC:

894

AN:

4822

European-Finnish (FIN)

AF:

0.451

AC:

4758

AN:

10552

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.368

AC:

24972

AN:

67922

Other (OTH)

AF:

0.283

AC:

597

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1634

3268

4903

6537

8171

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

476

952

1428

1904

2380

<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:

0.342

Hom.:

4010

Bravo

AF:

0.303

TwinsUK

AF:

0.374

AC:

1386

ALSPAC

AF:

0.368

AC:

1417

ESP6500AA

AF:

0.246

AC:

1083

ESP6500EA

AF:

0.361

AC:

3103

ExAC

AF:

0.313

AC:

37956

Asia WGS

AF:

0.175

AC:

606

AN:

3478

EpiCase

AF:

0.330

EpiControl

AF:

0.325

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.61

D;T;T

Eigen

Pathogenic

0.74

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

D;.;D

MetaRNN

Benign

0.0042

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Pathogenic

3.5

.;M;M

PhyloP100

7.9

PrimateAI

Uncertain

0.53

PROVEAN

Pathogenic

-5.6

D;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.012

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.17

MPC

0.43

ClinPred

0.027

GERP RS

5.0

Varity_R

0.85

gMVP

0.37

Mutation Taster

=84/16

polymorphism (auto)

(source)

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

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