Variant 16-28607070-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001055.4(SULT1A1):c.380A>G(p.Tyr127Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 36)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SULT1A1
NM_001055.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.33

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULT1A1	NM_001055.4 linkuse as main transcript	c.380A>G	p.Tyr127Cys	missense_variant	5/8	ENST00000314752.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULT1A1	ENST00000314752.12 linkuse as main transcript	c.380A>G	p.Tyr127Cys	missense_variant	5/8	1	NM_001055.4	P1	P50225-1
SULT1A1	ENST00000569554.5 linkuse as main transcript	c.380A>G	p.Tyr127Cys	missense_variant	4/7	1		P1	P50225-1
SULT1A1	ENST00000566189.5 linkuse as main transcript	c.380A>G	p.Tyr127Cys	missense_variant	5/8	5
SULT1A1	ENST00000567512.1 linkuse as main transcript	c.254A>G	p.Tyr85Cys	missense_variant	4/6	3

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460394

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726518

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151878

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74186

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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

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 08, 2023

The c.380A>G (p.Y127C) alteration is located in exon 5 (coding exon 4) of the SULT1A1 gene. This alteration results from a A to G substitution at nucleotide position 380, causing the tyrosine (Y) at amino acid position 127 to be replaced by a cysteine (C). 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

0.31

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.070

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.79

D;.;D;D;D;.;D

Eigen

Uncertain

0.24

Eigen_PC

Benign

0.0046

FATHMM_MKL

Uncertain

0.93

M_CAP

Benign

0.0044

MetaRNN

Pathogenic

0.89

D;D;D;D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.7

H;.;H;H;H;.;.

MutationTaster

Benign

0.92

D;D;D;D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-8.7

D;D;D;D;D;D;D

Sift

Uncertain

0.0060

D;D;D;D;D;D;D

Sift4G

Uncertain

0.025

D;D;D;D;D;.;.

Polyphen

0.99

D;D;D;D;D;.;.

Vest4

0.80

MutPred

0.68

Loss of methylation at K122 (P = 0.0666);.;Loss of methylation at K122 (P = 0.0666);Loss of methylation at K122 (P = 0.0666);Loss of methylation at K122 (P = 0.0666);Loss of methylation at K122 (P = 0.0666);.;

MVP

0.53

MPC

0.070

ClinPred

1.0

GERP RS

1.2

Varity_R

0.92

gMVP

0.81

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