chr7-66240792-C-G

Position:

• chr7-66240792-C-G

Variant summary

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

The NM_003596.4(TPST1):​c.367C>G​(p.Arg123Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TPST1 NM_003596.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.66

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]

TPST1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPST1	NM_003596.4	c.367C>G	p.Arg123Gly	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.367C>G	p.Arg123Gly	missense_variant	2/6	1	NM_003596.4	ENSP00000302413.5
TPST1	ENST00000480281.5	n.189+35270C>G		intron_variant		1
TPST1	ENST00000649664.1	c.367C>G	p.Arg123Gly	missense_variant	3/7			ENSP00000497281.1
TPST1	ENST00000451388.1	c.367C>G	p.Arg123Gly	missense_variant	2/2	4		ENSP00000391338.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461890 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.0000166

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

Aug 20, 2024

The c.367C>G (p.R123G) alteration is located in exon 2 (coding exon 1) of the TPST1 gene. This alteration results from a C to G substitution at nucleotide position 367, causing the arginine (R) at amino acid position 123 to be replaced by a glycine (G). 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	1.0
BayesDel_addAF	Pathogenic	0.41	D
BayesDel_noAF	Pathogenic	0.36
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	D;D;.
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.66
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	.;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Uncertain	2.8	M;M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.3	D;.;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0030	D;.;D
Sift4G	Benign	0.068	T;.;D
Polyphen		1.0	D;D;.
Vest4		0.87
MutPred		0.56		Loss of MoRF binding (P = 0.02);Loss of MoRF binding (P = 0.02);Loss of MoRF binding (P = 0.02);
MVP		0.30
MPC		1.1
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.91
gMVP		0.94

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: chr7-65705779;