rs749565589

Variant summary

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

The NM_001054.4(SULT1A2):​c.565C>T​(p.Leu189Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L189I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

SULT1A2
NM_001054.4 missense

Scores

2
8
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.78
Variant links:
Genes affected
SULT1A2 (HGNC:11454): (sulfotransferase family 1A member 2) 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. Two alternatively spliced variants that encode the same protein have been described. [provided by RefSeq, Jul 2008]

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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, 0.915

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SULT1A2NM_001054.4 linkc.565C>T p.Leu189Phe missense_variant Exon 6 of 8 ENST00000335715.9 NP_001045.2 P50226

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SULT1A2ENST00000335715.9 linkc.565C>T p.Leu189Phe missense_variant Exon 6 of 8 1 NM_001054.4 ENSP00000338742.4 P50226

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
Asia WGS
AF:
0.000289
AC:
1
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Benign
-0.035
T
BayesDel_noAF
Benign
-0.29
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.49
T;T;D
Eigen
Pathogenic
0.69
Eigen_PC
Uncertain
0.63
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.84
.;T;D
M_CAP
Benign
0.0086
T
MetaRNN
Pathogenic
0.91
D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.8
M;M;.
PrimateAI
Benign
0.48
T
PROVEAN
Uncertain
-3.8
D;D;D
REVEL
Benign
0.27
Sift
Uncertain
0.012
D;D;D
Sift4G
Uncertain
0.043
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.39
MutPred
0.84
Loss of stability (P = 0.2202);Loss of stability (P = 0.2202);Loss of stability (P = 0.2202);
MVP
0.55
MPC
0.44
ClinPred
0.99
D
GERP RS
4.7
Varity_R
0.53
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs749565589; hg19: chr16-28604602; API