7-66240969-A-G

Position:

• chr7-66240969-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003596.4(TPST1):​c.544A>G​(p.Met182Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TPST1 NM_003596.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.96

Genes affected

TPST1 (HGNC:12020): (tyrosylprotein sulfotransferase 1) Enables protein homodimerization activity and protein-tyrosine sulfotransferase activity. Involved in peptidyl-tyrosine sulfation. Is integral component of Golgi membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.879

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPST1	NM_003596.4	c.544A>G	p.Met182Val	missense_variant	2/6	ENST00000304842.6	NP_003587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPST1	ENST00000304842.6	c.544A>G	p.Met182Val	missense_variant	2/6	1	NM_003596.4	ENSP00000302413	P1
TPST1	ENST00000480281.5	n.189+35447A>G		intron_variant, non_coding_transcript_variant		1
TPST1	ENST00000649664.1	c.544A>G	p.Met182Val	missense_variant	3/7			ENSP00000497281	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Dec 14, 2021

The c.544A>G (p.M182V) alteration is located in exon 2 (coding exon 1) of the TPST1 gene. This alteration results from a A to G substitution at nucleotide position 544, causing the methionine (M) at amino acid position 182 to be replaced by a valine (V). 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	Pathogenic	0.65
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.65	D;D
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	.;D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.88	D;D
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.1	M;M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.74	T
PROVEAN	Uncertain	-4.0	D;.
REVEL	Uncertain	0.44
Sift	Benign	0.045	D;.
Sift4G	Uncertain	0.0070	D;.
Polyphen		0.98	D;D
Vest4		0.83
MutPred		0.68		Loss of MoRF binding (P = 0.1143);Loss of MoRF binding (P = 0.1143);
MVP		0.56
MPC		0.94
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.68
gMVP		0.84

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: chr7-65705956;