22-26541506-C-G

Variant names:

• chr22-26541506-C-G
• rs377741619
• NM_003595.5:c.125G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003595.5(TPST2):​c.125G>C​(p.Arg42Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R42Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TPST2 NM_003595.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.00
• Publications: 1 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08968702).

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.125G>C	p.Arg42Pro	missense	Exon 3 of 7	NP_003586.3
	TPST2	NM_001362923.2		c.287G>C	p.Arg96Pro	missense	Exon 4 of 8	NP_001349852.1
	TPST2	NM_001008566.3		c.125G>C	p.Arg42Pro	missense	Exon 3 of 7	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.125G>C	p.Arg42Pro	missense	Exon 3 of 7	ENSP00000339813.4	O60704
	TPST2	ENST00000910417.1		c.125G>C	p.Arg42Pro	missense	Exon 3 of 7	ENSP00000580476.1
	TPST2	ENST00000398110.6	TSL:2	c.125G>C	p.Arg42Pro	missense	Exon 3 of 7	ENSP00000381180.2	O60704

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	0.0015	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Benign	0.72
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		3.0
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.13
Sift	Benign	0.35	T
Sift4G	Benign	0.29	T
Polyphen		0.076	B
Vest4		0.48
MutPred		0.39		Loss of solvent accessibility (P = 8e-04)
MVP		0.18
MPC		0.85
ClinPred		0.27	T
GERP RS		1.7
Varity_R		0.17
gMVP		0.59
Mutation Taster		=81/19	polymorphism

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: rs377741619; hg19: chr22-26937472;