Variant 16-28605867-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001055.4(SULT1A1):c.842C>T(p.Ala281Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000856 in 151,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000086 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000056 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

SULT1A1
NM_001055.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0870

Variant links:

Genes affected

SULT1A1 (HGNC:11453): (sulfotransferase family 1A member 1) 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. Multiple alternatively spliced variants that encode two isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

SULT1A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13223872).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULT1A1	NM_001055.4 linkuse as main transcript	c.842C>T	p.Ala281Val	missense_variant	8/8	ENST00000314752.12	NP_001046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULT1A1	ENST00000314752.12 linkuse as main transcript	c.842C>T	p.Ala281Val	missense_variant	8/8	1	NM_001055.4	ENSP00000321988	P1	P50225-1
SULT1A1	ENST00000569554.5 linkuse as main transcript	c.842C>T	p.Ala281Val	missense_variant	7/7	1		ENSP00000457912	P1	P50225-1
SULT1A1	ENST00000566189.5 linkuse as main transcript	c.842C>T	p.Ala281Val	missense_variant	8/8	5		ENSP00000456459

Frequencies

GnomAD3 genomes

AF:

0.0000857

AC:

AN:

151726

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

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:

0.0000147

Gnomad OTH

AF:

0.000482

GnomAD3 exomes

AF:

0.0000564

AC:

AN:

248440

Hom.:

AF XY:

0.0000595

AC XY:

AN XY:

134400

show subpopulations

Gnomad AFR exome

AF:

0.000437

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000658

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000447

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000556

AC:

AN:

1457670

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

725104

show subpopulations

Gnomad4 AFR exome

AF:

0.000509

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.0000831

GnomAD4 genome

AF:

0.0000856

AC:

AN:

151844

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000477

Alfa

AF:

0.000422

Hom.:

ExAC

AF:

0.0000907

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

Dec 18, 2023

The c.842C>T (p.A281V) alteration is located in exon 8 (coding exon 7) of the SULT1A1 gene. This alteration results from a C to T substitution at nucleotide position 842, causing the alanine (A) at amino acid position 281 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

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Uncertain

0.49

T;.;T;T;T;.

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.080

LIST_S2

Benign

0.54

.;T;T;.;.;D

M_CAP

Benign

0.036

MetaRNN

Benign

0.089

T;T;T;T;T;T

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.5

M;.;M;M;M;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.8

N;N;N;N;N;N

REVEL

Benign

0.22

Sift

Benign

0.061

T;T;T;T;T;T

Sift4G

Uncertain

0.049

D;T;D;D;D;.

Polyphen

0.0060

B;B;B;B;B;.

Vest4

0.059

MVP

0.84

MPC

1.5

ClinPred

0.043

GERP RS

0.97

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.43

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