rs1433304876

Variant names:

• chr7-66240984-C-G
• rs1433304876
• NM_003596.4:c.559C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-66240984-C-G
• chr7-66240984-C-T

Variant summary

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

The NM_003596.4(TPST1):​c.559C>G​(p.Arg187Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R187Q) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: TPST1 NM_003596.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.03

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, 0.909

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TPST1	NM_003596.4	c.559C>G	p.Arg187Gly	missense_variant	Exon 2 of 6	ENST00000304842.6	NP_003587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TPST1	ENST00000304842.6	c.559C>G	p.Arg187Gly	missense_variant	Exon 2 of 6	1	NM_003596.4	ENSP00000302413.5
TPST1	ENST00000480281.5	n.189+35462C>G		intron_variant	Intron 1 of 4	1
TPST1	ENST00000649664.1	c.559C>G	p.Arg187Gly	missense_variant	Exon 3 of 7			ENSP00000497281.1
TPST1	ENST00000451388.1	c.*137C>G		downstream_gene_variant		4		ENSP00000391338.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152140 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74314

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.72	D;D
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.81
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	.;D
M_CAP	Benign	0.051	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	0.018	D
MutationAssessor	Pathogenic	3.6	H;H
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-7.0	D;.
REVEL	Uncertain	0.52
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.0030	D;.
Polyphen		1.0	D;D
Vest4		0.92
MutPred		0.73		Loss of methylation at R187 (P = 0.0097);Loss of methylation at R187 (P = 0.0097);
MVP		0.70
MPC		1.1
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.97
gMVP		0.96

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: rs1433304876; hg19: chr7-65705971;