Variant chr2-37167981-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000535679.6(SULT6B1):c.866C>T(p.Thr289Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000438 in 1,599,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T289S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

SULT6B1
ENST00000535679.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.41

Variant links:

Genes affected

SULT6B1 (HGNC:33433): (sulfotransferase family 6B member 1) Predicted to enable sulfotransferase activity. Predicted to be involved in sulfation. Predicted to be located in cytosol. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SULT6B1 links:

Genome browser will be placed here

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/exons	MANE	Protein	UniProt
SULT6B1	NM_001367551.1 linkuse as main transcript	c.866C>T	p.Thr289Ile	missense_variant	7/7	ENST00000535679.6	NP_001354480.1
SULT6B1	NM_001032377.2 linkuse as main transcript	c.752C>T	p.Thr251Ile	missense_variant	9/9		NP_001027549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULT6B1	ENST00000535679.6 linkuse as main transcript	c.866C>T	p.Thr289Ile	missense_variant	7/7	1	NM_001367551.1	ENSP00000444081	P1	Q6IMI4-1
SULT6B1	ENST00000407963.2 linkuse as main transcript	c.752C>T	p.Thr251Ile	missense_variant	8/8	5		ENSP00000384950
SULT6B1	ENST00000689208.1 linkuse as main transcript	c.*636C>T		3_prime_UTR_variant, NMD_transcript_variant	7/7			ENSP00000510164
SULT6B1	ENST00000692190.1 linkuse as main transcript	c.*408C>T		3_prime_UTR_variant, NMD_transcript_variant	7/7			ENSP00000509090

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000845

AC:

AN:

236752

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128660

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000595

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000907

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1447794

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

720382

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.0000168

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 07, 2022

The c.752C>T (p.T251I) alteration is located in exon 7 (coding exon 7) of the SULT6B1 gene. This alteration results from a C to T substitution at nucleotide position 752, causing the threonine (T) at amino acid position 251 to be replaced by an isoleucine (I). 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

Pathogenic

0.59

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;.

Eigen

Benign

0.079

Eigen_PC

Benign

-0.025

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.010

MetaRNN

Uncertain

0.56

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.6

M;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-5.0

D;D

REVEL

Benign

0.16

Sift

Uncertain

0.021

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.45

B;.

Vest4

0.48

MutPred

0.69

Gain of sheet (P = 0.0477);.;

MVP

0.055

ClinPred

0.89

GERP RS

3.5

Varity_R

0.67

gMVP

0.46

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over