rs1042028

Variant names:

• chr16-28606193-C-T
• rs1042028
• NM_001055.4:c.638G>A

Variant summary

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

The NM_001055.4(SULT1A1):​c.638G>A​(p.Arg213His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,484,706 control chromosomes in the GnomAD database, including 93,546 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R213C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.30 (7555 hom., cov: 34)
  • Exomes 𝑓: 0.31 (85991 hom.)
• Consequence: SULT1A1 NM_001055.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 25 publications found

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]

ENSG00000289755 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036977232).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1A1	NM_001055.4	c.638G>A	p.Arg213His	missense_variant	Exon 7 of 8	ENST00000314752.12	NP_001046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT1A1	ENST00000314752.12	c.638G>A	p.Arg213His	missense_variant	Exon 7 of 8	1	NM_001055.4	ENSP00000321988.7

Frequencies

GnomAD3 genomes AF: 0.295 AC: 43869 AN: 148526 Hom.: 7546 Cov.: 34

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.0676

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.259

GnomAD2 exomes AF: 0.224 AC: 46101 AN: 206082 AF XY: 0.214

Gnomad AFR exome AF: 0.170

Gnomad AMR exome AF: 0.318

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.0389

Gnomad FIN exome AF: 0.379

Gnomad NFE exome AF: 0.242

Gnomad OTH exome AF: 0.231

GnomAD4 exome AF: 0.307 AC: 410105 AN: 1336078 Hom.: 85991 Cov.: 83 AF XY: 0.303 AC XY: 201581 AN XY: 665188

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.209 AC: 6357 AN: 30458

American (AMR) AF: 0.372 AC: 15559 AN: 41788

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 5496 AN: 24308

East Asian (EAS) AF: 0.0918 AC: 3585 AN: 39070

South Asian (SAS) AF: 0.185 AC: 15260 AN: 82582

European-Finnish (FIN) AF: 0.428 AC: 21805 AN: 50968

Middle Eastern (MID) AF: 0.144 AC: 761 AN: 5302

European-Non Finnish (NFE) AF: 0.324 AC: 325550 AN: 1005490

Other (OTH) AF: 0.280 AC: 15732 AN: 56112

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.295 AC: 43911 AN: 148628 Hom.: 7555 Cov.: 34 AF XY: 0.295 AC XY: 21414 AN XY: 72468

African (AFR) AF: 0.236 AC: 9559 AN: 40464

American (AMR) AF: 0.318 AC: 4746 AN: 14922

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 819 AN: 3392

East Asian (EAS) AF: 0.0678 AC: 348 AN: 5134

South Asian (SAS) AF: 0.191 AC: 904 AN: 4740

European-Finnish (FIN) AF: 0.434 AC: 4454 AN: 10270

Middle Eastern (MID) AF: 0.157 AC: 44 AN: 280

European-Non Finnish (NFE) AF: 0.337 AC: 22392 AN: 66470

Other (OTH) AF: 0.256 AC: 525 AN: 2052

Alfa AF: 0.317 Hom.: 1515

ESP6500AA AF: 0.182 AC: 798

ESP6500EA AF: 0.270 AC: 2322

ExAC AF: 0.241 AC: 29256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	D;.;D;D;D;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.12	.;T;T;.;.;T
MetaRNN	Benign	0.0037	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;.;L;L;L;.
PhyloP100		1.0
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.9	D;D;D;D;D;D
REVEL	Uncertain	0.34
Sift	Benign	0.052	T;T;T;T;T;T
Sift4G	Benign	0.072	T;T;T;T;T;.
Polyphen		0.030	B;B;B;B;B;.
Vest4		0.050
MPC		1.8
ClinPred		0.011	T
GERP RS		2.2
Varity_R		0.31
gMVP		0.41
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1042028; hg19: chr16-28617514; COSMIC: COSV59086332; COSMIC: COSV59086332;