dbSNP rs1975350: SULT1A3:p.Gln35Gln (chr16-30200833-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_177552.4(SULT1A3):c.105A>G(p.Gln35Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 2685 hom., cov: 6)

Exomes 𝑓: 0.36 ( 11172 hom. )

Consequence

SULT1A3
NM_177552.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.31

Variant links:

Genes affected

SULT1A3 (HGNC:11455): (sulfotransferase family 1A member 3) 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 a phenol sulfotransferase with thermolabile enzyme activity. Four sulfotransferase genes are located on the p arm of chromosome 16; this gene and SULT1A4 arose from a segmental duplication. This gene is the most centromeric of the four sulfotransferase genes. Read-through transcription exists between this gene and the upstream SLX1A (SLX1 structure-specific endonuclease subunit homolog A) gene that encodes a protein containing GIY-YIG domains. [provided by RefSeq, Nov 2010]

SULT1A3 links:

SLX1A-SULT1A3 (HGNC:44437): (SLX1A-SULT1A3 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring SLX1A (SLX1 structure-specific endonuclease subunit homolog A) and SULT1A3 (sulfotransferase family, cytosolic, 1A, phenol-preferring, member 3) genes on the short arm of chromosome 16. A duplicate read-through locus also exists between the SLX1B and SULT1A4 genes located approximately 730 kb upstream on the same chromosome. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2017]

SLX1A-SULT1A3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP7

Synonymous conserved (PhyloP=-2.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1A3	NM_177552.4 link	c.105A>G	p.Gln35Gln	synonymous_variant	Exon 2 of 8	ENST00000338971.10	NP_808220.1	P0DMM9-1P0DMN0Q1ET61
SLX1A-SULT1A3	NR_037608.1 link	n.1026A>G		non_coding_transcript_exon_variant	Exon 5 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT1A3	ENST00000338971.10 link	c.105A>G	p.Gln35Gln	synonymous_variant	Exon 2 of 8	1	NM_177552.4	ENSP00000343645.6		P0DMM9-1

Frequencies

GnomAD3 genomes

AF:

0.400

AC:

15664

AN:

39152

Hom.:

2688

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.0883

Gnomad SAS

AF:

0.335

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.413

GnomAD3 exomes

AF:

0.258

AC:

14906

AN:

57808

Hom.:

331

AF XY:

0.265

AC XY:

7625

AN XY:

28826

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.303

Gnomad EAS exome

AF:

0.0670

Gnomad SAS exome

AF:

0.274

Gnomad FIN exome

AF:

0.332

Gnomad NFE exome

AF:

0.372

Gnomad OTH exome

AF:

0.301

GnomAD4 exome

AF:

0.360

AC:

276167

AN:

766484

Hom.:

11172

Cov.:

AF XY:

0.358

AC XY:

137742

AN XY:

384674

show subpopulations

Gnomad4 AFR exome

AF:

0.161

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.306

Gnomad4 EAS exome

AF:

0.104

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.318

Gnomad4 NFE exome

AF:

0.391

Gnomad4 OTH exome

AF:

0.339

GnomAD4 genome

AF:

0.400

AC:

15655

AN:

39168

Hom.:

2685

Cov.:

AF XY:

0.395

AC XY:

7001

AN XY:

17736

show subpopulations

Gnomad4 AFR

AF:

0.248

Gnomad4 AMR

AF:

0.303

Gnomad4 ASJ

AF:

0.332

Gnomad4 EAS

AF:

0.0877

Gnomad4 SAS

AF:

0.332

Gnomad4 FIN

AF:

0.405

Gnomad4 NFE

AF:

0.459

Gnomad4 OTH

AF:

0.404

Alfa

AF:

0.363

Hom.:

878

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.35

DANN

Benign

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over