Variant 16-28605868-C-T 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_001055.4(SULT1A1):c.841G>A(p.Ala281Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,457,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

SULT1A1
NM_001055.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.145

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:

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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=0.20110106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULT1A1	NM_001055.4 linkuse as main transcript	c.841G>A	p.Ala281Thr	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.841G>A	p.Ala281Thr	missense_variant	8/8	1	NM_001055.4	ENSP00000321988	P1	P50225-1
SULT1A1	ENST00000569554.5 linkuse as main transcript	c.841G>A	p.Ala281Thr	missense_variant	7/7	1		ENSP00000457912	P1	P50225-1
SULT1A1	ENST00000566189.5 linkuse as main transcript	c.841G>A	p.Ala281Thr	missense_variant	8/8	5		ENSP00000456459

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

248802

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134592

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1457912

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

725258

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Dec 20, 2023

The c.841G>A (p.A281T) alteration is located in exon 8 (coding exon 7) of the SULT1A1 gene. This alteration results from a G to A substitution at nucleotide position 841, causing the alanine (A) at amino acid position 281 to be replaced by a threonine (T). 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

0.088

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Benign

8.6

DANN

Benign

0.95

DEOGEN2

Benign

0.36

T;.;T;T;T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.81

.;T;T;.;.;D

M_CAP

Benign

0.028

MetaRNN

Benign

0.12

T;T;T;T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.6

L;.;L;L;L;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.97

N;N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.098

T;T;T;T;T;T

Sift4G

Benign

0.13

T;T;T;T;T;.

Polyphen

0.0

B;B;B;B;B;.

Vest4

0.10

MutPred

0.32

Gain of phosphorylation at A281 (P = 0.0618);.;Gain of phosphorylation at A281 (P = 0.0618);Gain of phosphorylation at A281 (P = 0.0618);Gain of phosphorylation at A281 (P = 0.0618);Gain of phosphorylation at A281 (P = 0.0618);

MVP

0.81

MPC

1.5

ClinPred

0.080

GERP RS

0.99

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.37

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