16-28592087-C-T

Variant summary

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

The NM_001054.4(SULT1A2):​c.829G>A​(p.Asp277Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,611,980 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: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

SULT1A2
NM_001054.4 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.65
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]

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, 0.859

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SULT1A2NM_001054.4 linkc.829G>A p.Asp277Asn missense_variant Exon 8 of 8 ENST00000335715.9 NP_001045.2 P50226

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SULT1A2ENST00000335715.9 linkc.829G>A p.Asp277Asn missense_variant Exon 8 of 8 1 NM_001054.4 ENSP00000338742.4 P50226

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152218
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000723
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250766
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135642
show subpopulations
Gnomad AFR exome
AF:
0.0000618
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:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000185
AC:
27
AN:
1459762
Hom.:
0
Cov.:
80
AF XY:
0.0000207
AC XY:
15
AN XY:
726174
show subpopulations
Gnomad4 AFR exome
AF:
0.000150
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:
0.0000171
Gnomad4 OTH exome
AF:
0.0000498
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152218
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74356
show subpopulations
Gnomad4 AFR
AF:
0.0000723
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:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000340
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.829G>A (p.D277N) alteration is located in exon 8 (coding exon 7) of the SULT1A2 gene. This alteration results from a G to A substitution at nucleotide position 829, causing the aspartic acid (D) at amino acid position 277 to be replaced by an asparagine (N). 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
0.22
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.27
CADD
Benign
16
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.53
D;T;T
Eigen
Benign
-0.037
Eigen_PC
Benign
0.035
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.88
D;.;D
M_CAP
Benign
0.025
T
MetaRNN
Pathogenic
0.86
D;D;D
MetaSVM
Uncertain
-0.027
T
MutationAssessor
Uncertain
2.6
.;M;M
PrimateAI
Benign
0.35
T
PROVEAN
Uncertain
-3.2
D;D;D
REVEL
Uncertain
0.46
Sift
Uncertain
0.0080
D;T;T
Sift4G
Benign
0.11
T;T;T
Polyphen
0.044
.;B;B
Vest4
0.27
MutPred
0.86
.;Loss of ubiquitination at K282 (P = 0.0432);Loss of ubiquitination at K282 (P = 0.0432);
MVP
0.83
MPC
1.4
ClinPred
0.60
D
GERP RS
4.6
Varity_R
0.31
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.

Other links and lift over

dbSNP: rs371745843; hg19: chr16-28603408; API