rs1136703

Positions:

• chr16-28595911-A-C
• chr16-28595911-A-G
• chr16-28595911-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001054.4(SULT1A2):​c.20T>G​(p.Ile7Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. I7T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SULT1A2 NM_001054.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.667

Genes affected

SULT1A2 (HGNC:11454): (sulfotransferase family 1A member 2) 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. Two alternatively spliced variants that encode the same protein have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04753086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULT1A2	NM_001054.4	c.20T>G	p.Ile7Ser	missense_variant	2/8	ENST00000335715.9	NP_001045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULT1A2	ENST00000335715.9	c.20T>G	p.Ile7Ser	missense_variant	2/8	1	NM_001054.4	ENSP00000338742	P1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1380510 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 686792

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.041
DANN	Benign	0.58
DEOGEN2	Benign	0.0089	T;T;T;T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.0059	T;.;T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.048	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.69	.;N;N;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.12	N;N;N;N
REVEL	Benign	0.023
Sift	Benign	0.36	T;T;T;T
Sift4G	Uncertain	0.056	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.074
MutPred		0.45		Gain of disorder (P = 0.011);Gain of disorder (P = 0.011);Gain of disorder (P = 0.011);Gain of disorder (P = 0.011);
MVP		0.11
MPC		0.10
ClinPred		0.16	T
GERP RS		-4.5
Varity_R		0.034
gMVP		0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1136703; hg19: chr16-28607232;