NM_001054.4:c.20T>C

Variant names:

• chr16-28595911-A-G
• rs1136703
• NM_001054.4:c.20T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001054.4(SULT1A2):​c.20T>C​(p.Ile7Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 1,273,122 control chromosomes in the GnomAD database, including 90,374 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (7959 hom., cov: 29)
  • Exomes 𝑓: 0.24 (82415 hom.)
• Consequence: SULT1A2 NM_001054.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.667
• Publications: 29 publications found

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]

ENSG00000288656 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0042673945).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1A2	NM_001054.4	c.20T>C	p.Ile7Thr	missense_variant	Exon 2 of 8	ENST00000335715.9	NP_001045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT1A2	ENST00000335715.9	c.20T>C	p.Ile7Thr	missense_variant	Exon 2 of 8	1	NM_001054.4	ENSP00000338742.4

Frequencies

GnomAD3 genomes AF: 0.310 AC: 46667 AN: 150586 Hom.: 7947 Cov.: 29

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0696

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.284

GnomAD2 exomes AF: 0.0773 AC: 13567 AN: 175472 AF XY: 0.0709

Gnomad AFR exome AF: 0.0366

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.0704

Gnomad EAS exome AF: 0.00644

Gnomad FIN exome AF: 0.0960

Gnomad NFE exome AF: 0.0785

Gnomad OTH exome AF: 0.0914

GnomAD4 exome AF: 0.237 AC: 266492 AN: 1122416 Hom.: 82415 Cov.: 35 AF XY: 0.233 AC XY: 131687 AN XY: 564316

African (AFR) AF: 0.145 AC: 4146 AN: 28514

American (AMR) AF: 0.295 AC: 10781 AN: 36488

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 4546 AN: 22786

East Asian (EAS) AF: 0.0853 AC: 3323 AN: 38968

South Asian (SAS) AF: 0.137 AC: 10685 AN: 77876

European-Finnish (FIN) AF: 0.388 AC: 16903 AN: 43532

Middle Eastern (MID) AF: 0.133 AC: 482 AN: 3618

European-Non Finnish (NFE) AF: 0.249 AC: 204251 AN: 820962

Other (OTH) AF: 0.229 AC: 11375 AN: 49672

GnomAD4 genome AF: 0.310 AC: 46716 AN: 150706 Hom.: 7959 Cov.: 29 AF XY: 0.309 AC XY: 22700 AN XY: 73554

African (AFR) AF: 0.232 AC: 9534 AN: 41152

American (AMR) AF: 0.332 AC: 5040 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 933 AN: 3434

East Asian (EAS) AF: 0.0698 AC: 358 AN: 5130

South Asian (SAS) AF: 0.180 AC: 860 AN: 4768

European-Finnish (FIN) AF: 0.446 AC: 4638 AN: 10404

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24556 AN: 67370

Other (OTH) AF: 0.281 AC: 587 AN: 2090

Alfa AF: 0.243 Hom.: 1100

Bravo AF: 0.304

ExAC AF: 0.137 AC: 16356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	0.0020
DANN	Benign	0.20
DEOGEN2	Benign	0.0086	T;T;T;T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.0034	T;.;T;T
MetaRNN	Benign	0.0043	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-0.77	.;N;N;.
PhyloP100		-0.67
PrimateAI	Benign	0.40	T
PROVEAN	Benign	0.67	N;N;N;N
REVEL	Benign	0.013
Sift	Benign	0.63	T;T;T;T
Sift4G	Benign	0.49	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.013
MPC		0.088
ClinPred		0.00021	T
GERP RS		-4.5
PromoterAI		-0.012	Neutral
Varity_R		0.026
gMVP		0.62
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1136703; hg19: chr16-28607232; COSMIC: COSV57680856; COSMIC: COSV57680856;