16-28606164-C-T

Variant names:

• chr16-28606164-C-T
• rs1801030
• NM_001055.4:c.667G>A

Variant summary

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

The ENST00000314752.12(SULT1A1):​c.667G>A​(p.Val223Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 151,048 control chromosomes in the GnomAD database, including 64,762 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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 0.92 (64762 hom., cov: 33)
  • Exomes 𝑓: 0.99 (719019 hom.)
  • Failed GnomAD Quality Control
• Consequence: SULT1A1 ENST00000314752.12 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39
• Publications: 71 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=1.2043685E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000314752.12. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1A1	NM_001055.4	MANE Select	c.667G>A	p.Val223Met	missense	Exon 7 of 8	NP_001046.2
	SULT1A1	NM_001394421.1		c.667G>A	p.Val223Met	missense	Exon 10 of 11	NP_001381350.1
	SULT1A1	NM_001394422.1		c.667G>A	p.Val223Met	missense	Exon 9 of 10	NP_001381351.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1A1	ENST00000314752.12	TSL:1 MANE Select	c.667G>A	p.Val223Met	missense	Exon 7 of 8	ENSP00000321988.7
	SULT1A1	ENST00000569554.5	TSL:1	c.667G>A	p.Val223Met	missense	Exon 6 of 7	ENSP00000457912.1
	ENSG00000289755	ENST00000562058.5	TSL:1	n.1426G>A		non_coding_transcript_exon	Exon 9 of 10

Frequencies

GnomAD3 genomes AF: 0.923 AC: 139256 AN: 150932 Hom.: 64722 Cov.: 33

Gnomad AFR AF: 0.734

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.968

Gnomad ASJ AF: 0.992

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.943

GnomAD2 exomes AF: 0.980 AC: 240853 AN: 245678 AF XY: 0.986

Gnomad AFR exome AF: 0.722

Gnomad AMR exome AF: 0.984

Gnomad ASJ exome AF: 0.995

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.999

Gnomad OTH exome AF: 0.990

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.992 AC: 1448130 AN: 1459874 Hom.: 719019 Cov.: 96 AF XY: 0.993 AC XY: 721368 AN XY: 726316

African (AFR) AF: 0.731 AC: 24226 AN: 33162

American (AMR) AF: 0.982 AC: 43867 AN: 44668

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 25973 AN: 26114

East Asian (EAS) AF: 1.00 AC: 39695 AN: 39696

South Asian (SAS) AF: 0.999 AC: 86149 AN: 86206

European-Finnish (FIN) AF: 1.00 AC: 53404 AN: 53404

Middle Eastern (MID) AF: 0.990 AC: 5687 AN: 5746

European-Non Finnish (NFE) AF: 0.999 AC: 1109972 AN: 1110580

Other (OTH) AF: 0.981 AC: 59157 AN: 60298

GnomAD4 genome AF: 0.923 AC: 139352 AN: 151048 Hom.: 64762 Cov.: 33 AF XY: 0.926 AC XY: 68276 AN XY: 73754

African (AFR) AF: 0.734 AC: 30276 AN: 41254

American (AMR) AF: 0.968 AC: 14624 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.992 AC: 3424 AN: 3450

East Asian (EAS) AF: 1.00 AC: 5162 AN: 5162

South Asian (SAS) AF: 0.999 AC: 4769 AN: 4772

European-Finnish (FIN) AF: 1.00 AC: 10454 AN: 10454

Middle Eastern (MID) AF: 0.997 AC: 289 AN: 290

European-Non Finnish (NFE) AF: 0.999 AC: 67478 AN: 67560

Other (OTH) AF: 0.943 AC: 1964 AN: 2082

Alfa AF: 0.993 Hom.: 25140

Bravo AF: 0.911

ESP6500AA AF: 0.628 AC: 2759

ESP6500EA AF: 0.998 AC: 8576

ExAC AF: 0.970 AC: 117526

Asia WGS AF: 0.986 AC: 3425 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	12
DANN	Benign	0.95
DEOGEN2	Uncertain	0.56	D
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.000012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.4
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.12
Sift	Benign	0.093	T
Sift4G	Uncertain	0.058	T
Polyphen		0.073	B
Vest4		0.072
MPC		1.5
ClinPred		0.015	T
GERP RS		2.2
Varity_R		0.24
gMVP		0.58
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1801030; hg19: chr16-28617485; COSMIC: COSV107396113; COSMIC: COSV107396113;