chr22-26532717-G-T

Position:

• chr22-26532717-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003595.5(TPST2):​c.1070C>A​(p.Ala357Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TPST2 NM_003595.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.17

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17874736).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TPST2	NM_003595.5	c.1070C>A	p.Ala357Asp	missense_variant	5/7	ENST00000338754.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TPST2	ENST00000338754.9	c.1070C>A	p.Ala357Asp	missense_variant	5/7	1	NM_003595.5	P1
TPST2	ENST00000398110.6	c.1070C>A	p.Ala357Asp	missense_variant	5/7	2		P1
TPST2	ENST00000403880.5	c.1070C>A	p.Ala357Asp	missense_variant	6/8	5		P1
TPST2	ENST00000454778.6	c.1070C>A	p.Ala357Asp	missense_variant	5/7	4		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

The c.1070C>A (p.A357D) alteration is located in exon 5 (coding exon 3) of the TPST2 gene. This alteration results from a C to A substitution at nucleotide position 1070, causing the alanine (A) at amino acid position 357 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Benign	0.88
DEOGEN2	Benign	0.091	T;T;T
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.040
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.85	.;.;T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.13	N;N;N
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.19	N;N;N
REVEL	Benign	0.038
Sift	Benign	0.86	T;T;T
Sift4G	Benign	0.68	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.57
MutPred		0.26		Gain of disorder (P = 0.023);Gain of disorder (P = 0.023);Gain of disorder (P = 0.023);
MVP		0.043
MPC		0.88
ClinPred		0.74	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-26928683;