chr16-28606193-C-T

Position:

• chr16-28606193-C-T

Variant summary

Our verdict is Benign. Variant got -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. 12/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. 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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SULT1A1	NM_001055.4	c.638G>A	p.Arg213His	missense_variant	7/8	ENST00000314752.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULT1A1	ENST00000314752.12	c.638G>A	p.Arg213His	missense_variant	7/8	1	NM_001055.4	P1
SULT1A1	ENST00000569554.5	c.638G>A	p.Arg213His	missense_variant	6/7	1		P1
SULT1A1	ENST00000566189.5	c.638G>A	p.Arg213His	missense_variant	7/8	5
SULT1A1	ENST00000567512.1			downstream_gene_variant		3

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

GnomAD3 exomes AF: 0.224 AC: 46101 AN: 206082 Hom.: 10788 AF XY: 0.214 AC XY: 23666 AN XY: 110836

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 SAS exome AF: 0.129

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

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.372

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.0918

Gnomad4 SAS exome AF: 0.185

Gnomad4 FIN exome AF: 0.428

Gnomad4 NFE exome AF: 0.324

Gnomad4 OTH exome AF: 0.280

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

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.0678

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.256

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;.
MutationTaster	Benign	1.0	P;P;P;P;P
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1042028; hg19: chr16-28617514; COSMIC: COSV59086332; COSMIC: COSV59086332;