dbSNP rs4987024: SULT1A2:p.Tyr62Phe (chr16-28595639-T-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001054.4(SULT1A2):c.185A>T(p.Tyr62Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,614,102 control chromosomes in the GnomAD database, including 65 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0077 ( 6 hom., cov: 31)

Exomes 𝑓: 0.011 ( 59 hom. )

Consequence

SULT1A2
NM_001054.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.79

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005838901).

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1A2	NM_001054.4 link	c.185A>T	p.Tyr62Phe	missense_variant	Exon 3 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.185A>T	p.Tyr62Phe	missense_variant	Exon 3 of 8	1	NM_001054.4	ENSP00000338742.4		P50226

Frequencies

GnomAD3 genomes

AF:

0.00772

AC:

1174

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00771

Gnomad SAS

AF:

0.00830

Gnomad FIN

AF:

0.0160

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0115

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00961

AC:

2416

AN:

251448

AF XY:

0.00971

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.00614

Gnomad FIN exome

AF:

0.0164

Gnomad NFE exome

AF:

0.0128

Gnomad OTH exome

AF:

0.00946

GnomAD4 exome

AF:

0.0109

AC:

15996

AN:

1461874

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

7983

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.00188

AC:

AN:

33480

American (AMR)

AF:

0.00228

AC:

102

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00207

AC:

AN:

26136

East Asian (EAS)

AF:

0.00363

AC:

144

AN:

39700

South Asian (SAS)

AF:

0.00852

AC:

735

AN:

86256

European-Finnish (FIN)

AF:

0.0170

AC:

908

AN:

53420

Middle Eastern (MID)

AF:

0.00433

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0120

AC:

13372

AN:

1111994

Other (OTH)

AF:

0.00982

AC:

593

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

1042

2085

3127

4170

5212

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00774

AC:

1178

AN:

152228

Hom.:

Cov.:

AF XY:

0.00750

AC XY:

558

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00173

AC:

AN:

41536

American (AMR)

AF:

0.00314

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.00772

AC:

AN:

5178

South Asian (SAS)

AF:

0.00830

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0160

AC:

170

AN:

10602

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0115

AC:

781

AN:

68004

Other (OTH)

AF:

0.00899

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

116

175

233

291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00802

Hom.:

Bravo

AF:

0.00647

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00802

AC:

ExAC

AF:

0.0104

AC:

1268

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0101

EpiControl

AF:

0.0108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.28

T;T;T;T

Eigen

Benign

0.18

Eigen_PC

Benign

0.087

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.39

T;.;T;T

MetaRNN

Benign

0.0058

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;L;L;.

PhyloP100

2.8

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.9

N;N;N;N

REVEL

Benign

0.071

Sift

Uncertain

0.017

D;T;T;T

Sift4G

Benign

0.18

T;T;T;T

Polyphen

1.0

.;D;D;.

Vest4

0.23

MPC

0.40

ClinPred

0.024

GERP RS

3.5

Varity_R

0.39

gMVP

0.48

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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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rs4987024

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

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