NM_177552.4:c.105A>G

Variant names:

• chr16-30200833-A-G
• rs1975350
• NM_177552.4:c.105A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31
• Publications: 4 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177552.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1A3	NM_177552.4	MANE Select	c.105A>G	p.Gln35Gln	synonymous	Exon 2 of 8	NP_808220.1
	SLX1A-SULT1A3	NR_037608.1		n.1026A>G		non_coding_transcript_exon	Exon 5 of 11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT1A3	ENST00000338971.10	TSL:1 MANE Select	c.105A>G	p.Gln35Gln	synonymous	Exon 2 of 8	ENSP00000343645.6
	SULT1A3	ENST00000563322.5	TSL:1	c.105A>G	p.Gln35Gln	synonymous	Exon 1 of 7	ENSP00000454518.1
	SULT1A3	ENST00000395138.6	TSL:1	c.105A>G	p.Gln35Gln	synonymous	Exon 2 of 8	ENSP00000378570.2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 15664 AN: 39152 Hom.: 2688 Cov.: 6

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

GnomAD2 exomes AF: 0.258 AC: 14906 AN: 57808 AF XY: 0.265

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 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.: 11 AF XY: 0.358 AC XY: 137742 AN XY: 384674

African (AFR) AF: 0.161 AC: 1919 AN: 11952

American (AMR) AF: 0.233 AC: 4411 AN: 18958

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 4146 AN: 13530

East Asian (EAS) AF: 0.104 AC: 2648 AN: 25380

South Asian (SAS) AF: 0.283 AC: 13878 AN: 49024

European-Finnish (FIN) AF: 0.318 AC: 9118 AN: 28692

Middle Eastern (MID) AF: 0.326 AC: 764 AN: 2342

European-Non Finnish (NFE) AF: 0.391 AC: 228090 AN: 583602

Other (OTH) AF: 0.339 AC: 11193 AN: 33004

GnomAD4 genome AF: 0.400 AC: 15655 AN: 39168 Hom.: 2685 Cov.: 6 AF XY: 0.395 AC XY: 7001 AN XY: 17736

African (AFR) AF: 0.248 AC: 963 AN: 3880

American (AMR) AF: 0.303 AC: 1406 AN: 4646

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 426 AN: 1282

East Asian (EAS) AF: 0.0877 AC: 90 AN: 1026

South Asian (SAS) AF: 0.332 AC: 201 AN: 606

European-Finnish (FIN) AF: 0.405 AC: 739 AN: 1824

Middle Eastern (MID) AF: 0.405 AC: 34 AN: 84

European-Non Finnish (NFE) AF: 0.459 AC: 11399 AN: 24838

Other (OTH) AF: 0.404 AC: 215 AN: 532

Alfa AF: 0.363 Hom.: 878

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.39
PhyloP100		-2.3
PromoterAI		0.031	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1975350; hg19: chr16-30212154; COSMIC: COSV52148126; COSMIC: COSV52148126;