rs1801030

chr16-28606164-C-Achr16-28606164-C-Gchr16-28606164-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001055.4(SULT1A1):c.667G>T(p.Val223Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V223M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SULT1A1 NM_001055.4 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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULT1A1	NM_001055.4	c.667G>T	p.Val223Leu	missense_variant	7/8	ENST00000314752.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULT1A1	ENST00000314752.12	c.667G>T	p.Val223Leu	missense_variant	7/8	1	NM_001055.4	P1
SULT1A1	ENST00000569554.5	c.667G>T	p.Val223Leu	missense_variant	6/7	1		P1
SULT1A1	ENST00000566189.5	c.667G>T	p.Val223Leu	missense_variant	7/8	5
SULT1A1	ENST00000567512.1			downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 96

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
Cadd	Benign	19
Dann	Benign	0.94
DEOGEN2	Benign	0.32	T;.;T;T;T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.43	N
M_CAP	Benign	0.0033	T
MetaRNN	Uncertain	0.48	T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.0	L;.;L;L;L;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.84	N;N;N;N;N;N
Sift	Uncertain	0.0020	D;D;D;D;D;D
Sift4G	Uncertain	0.010	D;T;D;D;D;.
Polyphen		0.0040	B;B;B;B;B;.
Vest4		0.15
MutPred		0.75		Gain of helix (P = 0.132);.;Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.20
MPC		1.5
ClinPred		0.68	D
GERP RS		2.2
Varity_R		0.65
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.38		Position offset: -9

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;