Genetic Variant NM_001055.4:c.526G>T (chr16-28606829-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

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

The NM_001055.4(SULT1A1):c.526G>T(p.Val176Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000185 in 1,460,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 36)

Exomes 𝑓: 0.000018 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SULT1A1
NM_001055.4 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

ENSG00000289755 (HGNC:):

ENSG00000289755 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, 0.913

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1A1	NM_001055.4 link	c.526G>T	p.Val176Leu	missense_variant	Exon 6 of 8	ENST00000314752.12	NP_001046.2	P50225-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT1A1	ENST00000314752.12 link	c.526G>T	p.Val176Leu	missense_variant	Exon 6 of 8	1	NM_001055.4	ENSP00000321988.7		P50225-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151874

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

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:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1460512

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

726586

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

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:

0.0000216

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000198

AC:

AN:

151874

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:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000480

Hom.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.68

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

Eigen

Benign

0.10

Eigen_PC

Benign

0.013

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

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

M_CAP

Benign

0.028

MetaRNN

Pathogenic

0.91

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

MetaSVM

Benign

-0.32

MutationAssessor

Uncertain

2.5

M;.;M;M;M;.;.

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.9

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

REVEL

Uncertain

0.59

Sift

Uncertain

0.0010

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

Sift4G

Uncertain

0.0020

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

Polyphen

0.20

B;P;B;B;B;.;.

Vest4

0.67

MutPred

0.75

Loss of phosphorylation at Y173 (P = 0.1399);.;Loss of phosphorylation at Y173 (P = 0.1399);Loss of phosphorylation at Y173 (P = 0.1399);Loss of phosphorylation at Y173 (P = 0.1399);Loss of phosphorylation at Y173 (P = 0.1399);.;

MVP

0.81

MPC

0.015

ClinPred

0.97

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.87

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over