Variant 16-28605894-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001055.4(SULT1A1):c.815A>G(p.Gln272Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,609,054 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: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SULT1A1
NM_001055.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.34

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_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.965

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULT1A1	NM_001055.4 linkuse as main transcript	c.815A>G	p.Gln272Arg	missense_variant	8/8	ENST00000314752.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULT1A1	ENST00000314752.12 linkuse as main transcript	c.815A>G	p.Gln272Arg	missense_variant	8/8	1	NM_001055.4	P1	P50225-1
SULT1A1	ENST00000569554.5 linkuse as main transcript	c.815A>G	p.Gln272Arg	missense_variant	7/7	1		P1	P50225-1
SULT1A1	ENST00000566189.5 linkuse as main transcript	c.815A>G	p.Gln272Arg	missense_variant	8/8	5

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151708

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457346

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724824

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151708

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74060

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000148

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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 17, 2023

The c.815A>G (p.Q272R) alteration is located in exon 8 (coding exon 7) of the SULT1A1 gene. This alteration results from a A to G substitution at nucleotide position 815, causing the glutamine (Q) at amino acid position 272 to be replaced by an arginine (R). 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

Pathogenic

0.72

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Benign

-0.15

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.79

D;.;D;D;D;.

Eigen

Uncertain

0.40

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.0023

MetaRNN

Pathogenic

0.97

D;D;D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.9

H;.;H;H;H;.

MutationTaster

Benign

0.81

N;N;N;N;N

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.8

D;D;D;D;D;D

Sift

Uncertain

0.0010

D;D;D;D;D;D

Sift4G

Uncertain

0.0020

D;D;D;D;D;.

Polyphen

1.0

D;D;D;D;D;.

Vest4

0.72

MutPred

0.92

Gain of MoRF binding (P = 0.0243);.;Gain of MoRF binding (P = 0.0243);Gain of MoRF binding (P = 0.0243);Gain of MoRF binding (P = 0.0243);Gain of MoRF binding (P = 0.0243);

MVP

0.58

MPC

2.8

ClinPred

1.0

GERP RS

0.81

Varity_R

0.94

gMVP

0.91

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