Variant 2-37175197-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001367551.1(SULT6B1):c.559A>G(p.Ile187Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000126 in 1,590,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SULT6B1
NM_001367551.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.981

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07148233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULT6B1	NM_001367551.1 linkuse as main transcript	c.559A>G	p.Ile187Val	missense_variant	5/7	ENST00000535679.6	NP_001354480.1
SULT6B1	NM_001032377.2 linkuse as main transcript	c.445A>G	p.Ile149Val	missense_variant	7/9		NP_001027549.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULT6B1	ENST00000535679.6 linkuse as main transcript	c.559A>G	p.Ile187Val	missense_variant	5/7	1	NM_001367551.1	ENSP00000444081	P1	Q6IMI4-1
SULT6B1	ENST00000407963.2 linkuse as main transcript	c.445A>G	p.Ile149Val	missense_variant	6/8	5		ENSP00000384950
SULT6B1	ENST00000689208.1 linkuse as main transcript	c.*329A>G		3_prime_UTR_variant, NMD_transcript_variant	5/7			ENSP00000510164
SULT6B1	ENST00000692190.1 linkuse as main transcript	c.*167-3607A>G		intron_variant, NMD_transcript_variant				ENSP00000509090

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000415

AC:

AN:

240950

Hom.:

AF XY:

0.00000767

AC XY:

AN XY:

130428

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000560

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.95e-7

AC:

AN:

1438608

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

715024

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

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

May 30, 2023

The c.445A>G (p.I149V) alteration is located in exon 5 (coding exon 5) of the SULT6B1 gene. This alteration results from a A to G substitution at nucleotide position 445, causing the isoleucine (I) at amino acid position 149 to be replaced by a valine (V). 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

Benign

0.072

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

4.2

DANN

Benign

0.92

DEOGEN2

Benign

0.061

T;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.0085

MetaRNN

Benign

0.071

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.84

L;.

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.58

N;N

REVEL

Benign

0.12

Sift

Benign

0.54

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0

B;.

Vest4

0.13

MutPred

0.43

Loss of methylation at K191 (P = 0.101);.;

MVP

0.35

ClinPred

0.035

GERP RS

0.87

Varity_R

0.050

gMVP

0.19

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

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