rs12161068

chr22-26555249-T-Cchr22-26555249-T-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPST2	NM_003595.5	c.-160-10574A>G		intron_variant		ENST00000338754.9
MIR548J	NR_031615.1	n.75A>G		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPST2	ENST00000338754.9	c.-160-10574A>G		intron_variant		1	NM_003595.5	P1
MIR548J	ENST00000408833.1	n.75A>G		mature_miRNA_variant	1/1

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

GnomAD3 exomes AF: 0.00728 AC: 1781 AN: 244676 Hom.: 75 AF XY: 0.00525 AC XY: 700 AN XY: 133394

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 SAS exome AF: 0.000262

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

Gnomad4 AFR exome AF: 0.0934

Gnomad4 AMR exome AF: 0.00598

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000330

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000349

Gnomad4 OTH exome AF: 0.00524

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

Gnomad4 AFR AF: 0.0923

Gnomad4 AMR AF: 0.00888

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.00187 Hom.: 3

Bravo AF: 0.0308

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.1
Dann	Benign	0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs12161068; hg19: chr22-26951215;