NM_003595.5:c.-160-10544G>C

Variant names:

• chr22-26555219-C-G
• rs4822739
• NM_003595.5:c.-160-10544G>C

Variant summary

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

The NM_003595.5(TPST2):​c.-160-10544G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0834 in 533,524 control chromosomes in the GnomAD database, including 2,618 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 0.094 (938 hom., cov: 34)
  • Exomes 𝑓: 0.079 (1680 hom.)
• Consequence: TPST2 NM_003595.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.308
• Publications: 18 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPST2	NM_003595.5	c.-160-10544G>C		intron_variant	Intron 1 of 6	ENST00000338754.9	NP_003586.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPST2	ENST00000338754.9	c.-160-10544G>C		intron_variant	Intron 1 of 6	1	NM_003595.5	ENSP00000339813.4

Frequencies

GnomAD3 genomes AF: 0.0941 AC: 14314 AN: 152178 Hom.: 933 Cov.: 34

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0492

Gnomad OTH AF: 0.0961

GnomAD2 exomes AF: 0.0877 AC: 21601 AN: 246388 AF XY: 0.0866

Gnomad AFR exome AF: 0.159

Gnomad AMR exome AF: 0.119

Gnomad ASJ exome AF: 0.0748

Gnomad EAS exome AF: 0.208

Gnomad FIN exome AF: 0.0383

Gnomad NFE exome AF: 0.0486

Gnomad OTH exome AF: 0.0726

GnomAD4 exome AF: 0.0791 AC: 30169 AN: 381228 Hom.: 1680 Cov.: 0 AF XY: 0.0823 AC XY: 17875 AN XY: 217134

African (AFR) AF: 0.159 AC: 1669 AN: 10486

American (AMR) AF: 0.117 AC: 4259 AN: 36304

Ashkenazi Jewish (ASJ) AF: 0.0725 AC: 851 AN: 11744

East Asian (EAS) AF: 0.211 AC: 2776 AN: 13172

South Asian (SAS) AF: 0.128 AC: 8537 AN: 66718

European-Finnish (FIN) AF: 0.0383 AC: 1225 AN: 32006

Middle Eastern (MID) AF: 0.103 AC: 215 AN: 2092

European-Non Finnish (NFE) AF: 0.0490 AC: 9405 AN: 192066

Other (OTH) AF: 0.0740 AC: 1232 AN: 16640

GnomAD4 genome AF: 0.0941 AC: 14326 AN: 152296 Hom.: 938 Cov.: 34 AF XY: 0.0958 AC XY: 7137 AN XY: 74486

African (AFR) AF: 0.160 AC: 6634 AN: 41538

American (AMR) AF: 0.107 AC: 1641 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0749 AC: 260 AN: 3472

East Asian (EAS) AF: 0.215 AC: 1114 AN: 5182

South Asian (SAS) AF: 0.141 AC: 684 AN: 4834

European-Finnish (FIN) AF: 0.0372 AC: 395 AN: 10624

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0492 AC: 3348 AN: 68024

Other (OTH) AF: 0.0941 AC: 199 AN: 2114

Alfa AF: 0.0619 Hom.: 112

Bravo AF: 0.101

Asia WGS AF: 0.152 AC: 532 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.54
PhyloP100		-0.31
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: rs4822739; hg19: chr22-26951185; COSMIC: COSV58680032; COSMIC: COSV58680032;