chr16-28606164-C-T

Position:

• chr16-28606164-C-T

Variant summary

Our verdict is Benign. Variant got -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. 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.

• 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

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=1.2043685E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULT1A1	NM_001055.4	c.667G>A	p.Val223Met	missense_variant	7/8	ENST00000314752.12	NP_001046.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULT1A1	ENST00000314752.12	c.667G>A	p.Val223Met	missense_variant	7/8	1	NM_001055.4	ENSP00000321988	P1
SULT1A1	ENST00000569554.5	c.667G>A	p.Val223Met	missense_variant	6/7	1		ENSP00000457912	P1
SULT1A1	ENST00000566189.5	c.667G>A	p.Val223Met	missense_variant	7/8	5		ENSP00000456459
SULT1A1	ENST00000567512.1			downstream_gene_variant		3		ENSP00000455979

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

GnomAD3 exomes AF: 0.980 AC: 240853 AN: 245678 Hom.: 118691 AF XY: 0.986 AC XY: 131352 AN XY: 133226

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 SAS 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

Gnomad4 AFR exome AF: 0.731

Gnomad4 AMR exome AF: 0.982

Gnomad4 ASJ exome AF: 0.995

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.999

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.981

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

Gnomad4 AFR AF: 0.734

Gnomad4 AMR AF: 0.968

Gnomad4 ASJ AF: 0.992

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.943

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 v4.3

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;.;D;D;D;.
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.0036	N
LIST_S2	Benign	0.56	.;T;T;.;.;T
MetaRNN	Benign	0.000012	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M;.;M;M;M;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.5	N;N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.093	T;T;T;T;T;T
Sift4G	Uncertain	0.058	T;T;T;T;T;.
Polyphen		0.073	B;B;B;B;B;.
Vest4		0.072
MPC		1.5
ClinPred		0.015	T
GERP RS		2.2
Varity_R		0.24
gMVP		0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs1801030; hg19: chr16-28617485;