rs12161068

Variant names:

• chr22-26555249-T-C
• rs12161068
• NM_003595.5:c.-160-10574A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-26555249-T-C
• chr22-26555249-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003595.5(TPST2):​c.-160-10574A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 531,774 control chromosomes in the GnomAD database, including 227 homozygotes. 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 0.027 (171 hom., cov: 34)
  • Exomes 𝑓: 0.0036 (56 hom.)
• Consequence: TPST2 NM_003595.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 4 publications found

Genes affected

TPST2 (HGNC:12021): (tyrosylprotein sulfotransferase 2) The protein encoded by this gene catalyzes the O-sulfation of tyrosine residues within acidic regions of proteins. The encoded protein is a type II integral membrane protein found in the Golgi body. Alternative splicing produces multiple transcript variants encoding distinct isoforms. [provided by RefSeq, May 2018]

MIR548J (HGNC:35276): (microRNA 548j) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0899 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003595.5. 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
	TPST2	NM_003595.5	MANE Select	c.-160-10574A>G		intron	N/A	NP_003586.3
	TPST2	NM_001362923.2		c.-117-7631A>G		intron	N/A	NP_001349852.1
	TPST2	NM_001008566.3		c.-161+9975A>G		intron	N/A	NP_001008566.1	O60704

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPST2	ENST00000338754.9	TSL:1 MANE Select	c.-160-10574A>G		intron	N/A	ENSP00000339813.4	O60704
	TPST2	ENST00000910417.1		c.-160-10574A>G		intron	N/A	ENSP00000580476.1
	TPST2	ENST00000398110.6	TSL:2	c.-161+9975A>G		intron	N/A	ENSP00000381180.2	O60704

Frequencies

GnomAD3 genomes AF: 0.0265 AC: 4037 AN: 152246 Hom.: 167 Cov.: 34

Gnomad AFR AF: 0.0920

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00890

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0234

GnomAD2 exomes AF: 0.00728 AC: 1781 AN: 244676 AF XY: 0.00525

Gnomad AFR exome AF: 0.0974

Gnomad AMR exome AF: 0.00620

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000372

Gnomad OTH exome AF: 0.00348

GnomAD4 exome AF: 0.00363 AC: 1376 AN: 379410 Hom.: 56 Cov.: 0 AF XY: 0.00264 AC XY: 570 AN XY: 216292

African (AFR) AF: 0.0934 AC: 978 AN: 10474

American (AMR) AF: 0.00598 AC: 217 AN: 36302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11744

East Asian (EAS) AF: 0.00 AC: 0 AN: 13174

South Asian (SAS) AF: 0.000330 AC: 22 AN: 66684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30746

Middle Eastern (MID) AF: 0.00302 AC: 5 AN: 1654

European-Non Finnish (NFE) AF: 0.000349 AC: 67 AN: 192042

Other (OTH) AF: 0.00524 AC: 87 AN: 16590

GnomAD4 genome AF: 0.0266 AC: 4059 AN: 152364 Hom.: 171 Cov.: 34 AF XY: 0.0260 AC XY: 1937 AN XY: 74520

African (AFR) AF: 0.0923 AC: 3838 AN: 41580

American (AMR) AF: 0.00888 AC: 136 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000470 AC: 32 AN: 68034

Other (OTH) AF: 0.0232 AC: 49 AN: 2116

Alfa AF: 0.00582 Hom.: 16

Bravo AF: 0.0308

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.1
DANN	Benign	0.85
PhyloP100		0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs12161068; hg19: chr22-26951215;