16-28606829-C-T

Position:

chr16-28606829-C-T

Variant summary

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

The NM_001055.4(SULT1A1):c.526G>A(p.Val176Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 151,876 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 0.000020 ( 0 hom., cov: 36)

Exomes 𝑓: 0.000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SULT1A1
NM_001055.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.69

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 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, 0.864

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULT1A1	NM_001055.4 linkuse as main transcript	c.526G>A	p.Val176Met	missense_variant	6/8	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.526G>A	p.Val176Met	missense_variant	6/8	1	NM_001055.4	ENSP00000321988	P1	P50225-1
SULT1A1	ENST00000569554.5 linkuse as main transcript	c.526G>A	p.Val176Met	missense_variant	5/7	1		ENSP00000457912	P1	P50225-1
SULT1A1	ENST00000566189.5 linkuse as main transcript	c.526G>A	p.Val176Met	missense_variant	6/8	5		ENSP00000456459
SULT1A1	ENST00000567512.1 linkuse as main transcript	c.400G>A	p.Val134Met	missense_variant	5/6	3		ENSP00000455979

Frequencies

GnomAD3 genomes

AF:

0.0000198

AC:

AN:

151876

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251220

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000205

AC:

AN:

1460520

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726592

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000198

AC:

AN:

151876

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000416

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

Oct 12, 2022

The c.526G>A (p.V176M) alteration is located in exon 6 (coding exon 5) of the SULT1A1 gene. This alteration results from a G to A substitution at nucleotide position 526, causing the valine (V) at amino acid position 176 to be replaced by a methionine (M). 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

Uncertain

0.55

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.73

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

Eigen

Uncertain

0.41

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.86

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

M_CAP

Benign

0.021

MetaRNN

Pathogenic

0.86

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

MetaSVM

Uncertain

0.036

MutationAssessor

Pathogenic

3.6

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

MutationTaster

Benign

0.98

N;N;N;N;N

PrimateAI

Uncertain

0.71

PROVEAN

Uncertain

-2.9

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

REVEL

Uncertain

0.48

Sift

Uncertain

0.0020

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

Sift4G

Uncertain

0.0050

D;T;D;D;D;.;.

Polyphen

0.98

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

Vest4

0.83

MutPred

0.72

Gain of phosphorylation at Y173 (P = 0.1936);.;Gain of phosphorylation at Y173 (P = 0.1936);Gain of phosphorylation at Y173 (P = 0.1936);Gain of phosphorylation at Y173 (P = 0.1936);Gain of phosphorylation at Y173 (P = 0.1936);.;

MVP

0.86

MPC

0.022

ClinPred

0.96

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.80

gMVP

0.58

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