Genetic Variant SULT1C4:p.Asp5Glu (chr2-108378352-C-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_006588.4(SULT1C4):c.15C>G(p.Asp5Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,612,738 control chromosomes in the GnomAD database, including 75,108 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D5N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.39 ( 16119 hom., cov: 32)

Exomes 𝑓: 0.27 ( 58989 hom. )

Consequence

SULT1C4
NM_006588.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.874

Publications

44 publications found

Variant links:

Genes affected

SULT1C4 (HGNC:11457): (sulfotransferase family 1C member 4) 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 a protein that belongs to the SULT1 subfamily, responsible for transferring a sulfo moiety from PAPS to phenol-containing compounds. [provided by RefSeq, Jul 2008]

SULT1C4 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=9.924704E-7).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1C4	NM_006588.4 link	c.15C>G	p.Asp5Glu	missense_variant	Exon 1 of 7	ENST00000272452.7	NP_006579.2	O75897-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SULT1C4	ENST00000272452.7 link	c.15C>G	p.Asp5Glu	missense_variant	Exon 1 of 7	1	NM_006588.4	ENSP00000272452.2	O75897-1
SULT1C4	ENST00000409309.3 link	c.15C>G	p.Asp5Glu	missense_variant	Exon 1 of 5	1		ENSP00000387225.3	O75897-2
SULT1C4	ENST00000494122.1 link	n.442C>G		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes

AF:

0.392

AC:

59613

AN:

151918

Hom.:

16061

Cov.:

show subpopulations

Gnomad AFR

AF:

0.766

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.228

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.110

Gnomad SAS

AF:

0.425

Gnomad FIN

AF:

0.337

Gnomad MID

AF:

0.310

Gnomad NFE

AF:

0.241

Gnomad OTH

AF:

0.348

GnomAD2 exomes

AF:

0.283

AC:

71070

AN:

251050

AF XY:

0.287

show subpopulations

Gnomad AFR exome

AF:

0.782

Gnomad AMR exome

AF:

0.150

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.0712

Gnomad FIN exome

AF:

0.333

Gnomad NFE exome

AF:

0.245

Gnomad OTH exome

AF:

0.266

GnomAD4 exome

AF:

0.266

AC:

387856

AN:

1460702

Hom.:

58989

Cov.:

AF XY:

0.269

AC XY:

195320

AN XY:

726716

show subpopulations

African (AFR)

AF:

0.794

AC:

26561

AN:

33468

American (AMR)

AF:

0.163

AC:

7263

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

6397

AN:

26104

East Asian (EAS)

AF:

0.159

AC:

6315

AN:

39694

South Asian (SAS)

AF:

0.411

AC:

35429

AN:

86182

European-Finnish (FIN)

AF:

0.327

AC:

17471

AN:

53398

Middle Eastern (MID)

AF:

0.314

AC:

1806

AN:

5760

European-Non Finnish (NFE)

AF:

0.242

AC:

269244

AN:

1111062

Other (OTH)

AF:

0.288

AC:

17370

AN:

60348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

13369

26737

40106

53474

66843

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9352

18704

28056

37408

46760

<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:

0.393

AC:

59728

AN:

152036

Hom.:

16119

Cov.:

AF XY:

0.394

AC XY:

29323

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.767

AC:

31792

AN:

41464

American (AMR)

AF:

0.228

AC:

3484

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

860

AN:

3470

East Asian (EAS)

AF:

0.110

AC:

565

AN:

5152

South Asian (SAS)

AF:

0.424

AC:

2043

AN:

4818

European-Finnish (FIN)

AF:

0.337

AC:

3557

AN:

10570

Middle Eastern (MID)

AF:

0.313

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.241

AC:

16405

AN:

67956

Other (OTH)

AF:

0.355

AC:

750

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1402

2804

4207

5609

7011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

520

1040

1560

2080

2600

<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:

0.261

Hom.:

4709

Bravo

AF:

0.393

TwinsUK

AF:

0.250

AC:

926

ALSPAC

AF:

0.237

AC:

912

ESP6500AA

AF:

0.767

AC:

3378

ESP6500EA

AF:

0.246

AC:

2118

ExAC

AF:

0.298

AC:

36195

Asia WGS

AF:

0.379

AC:

1319

AN:

3478

EpiCase

AF:

0.242

EpiControl

AF:

0.244

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.26

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.0039

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0037

LIST_S2

Benign

0.14

T;T

MetaRNN

Benign

9.9e-7

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.55

N;N

PhyloP100

-0.87

PrimateAI

Benign

0.43

PROVEAN

Benign

0.71

N;N

REVEL

Benign

0.068

Sift

Benign

0.94

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.011

MutPred

0.062

Gain of helix (P = 0.0696);Gain of helix (P = 0.0696);

MPC

0.23

ClinPred

0.00089

GERP RS

-1.8

PromoterAI

-0.042

Neutral

(source)

Varity_R

0.078

gMVP

0.65

Mutation Taster

=99/1

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