Variant 16-28608732-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001055.4(SULT1A1):c.124C>G(p.Leu42Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,461,016 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

SULT1A1
NM_001055.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULT1A1	NM_001055.4 linkuse as main transcript	c.124C>G	p.Leu42Val	missense_variant	2/8	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.124C>G	p.Leu42Val	missense_variant	2/8	1	NM_001055.4	ENSP00000321988	P1	P50225-1
SULT1A1	ENST00000569554.5 linkuse as main transcript	c.124C>G	p.Leu42Val	missense_variant	1/7	1		ENSP00000457912	P1	P50225-1
SULT1A1	ENST00000566189.5 linkuse as main transcript	c.124C>G	p.Leu42Val	missense_variant	2/8	5		ENSP00000456459
SULT1A1	ENST00000567512.1 linkuse as main transcript	c.124C>G	p.Leu42Val	missense_variant	2/6	3		ENSP00000455979

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250916

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135614

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:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1461016

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726822

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:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 23, 2023

The c.124C>G (p.L42V) alteration is located in exon 2 (coding exon 1) of the SULT1A1 gene. This alteration results from a C to G substitution at nucleotide position 124, causing the leucine (L) at amino acid position 42 to be replaced by a valine (V). 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

0.17

BayesDel_addAF

Uncertain

0.091

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.28

T;T;T;T;.;T

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.78

.;T;.;.;T;T

M_CAP

Benign

0.044

MetaRNN

Uncertain

0.53

D;D;D;D;D;D

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

2.0

M;M;M;M;.;.

MutationTaster

Benign

0.52

D;D;D;D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.92

N;N;N;N;N;N

REVEL

Uncertain

0.50

Sift

Benign

0.27

T;T;T;T;T;T

Sift4G

Benign

0.26

T;T;T;T;.;.

Polyphen

0.026

B;B;B;B;.;.

Vest4

0.35

MutPred

0.64

Gain of catalytic residue at L42 (P = 0.1362);Gain of catalytic residue at L42 (P = 0.1362);Gain of catalytic residue at L42 (P = 0.1362);Gain of catalytic residue at L42 (P = 0.1362);Gain of catalytic residue at L42 (P = 0.1362);Gain of catalytic residue at L42 (P = 0.1362);

MVP

0.96

MPC

0.015

ClinPred

0.094

GERP RS

2.4

Varity_R

0.34

gMVP

0.65

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