chr7-66240969-A-G

Variant names:

• chr7-66240969-A-G
• NM_003596.4:c.544A>G

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003596.4. 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
	TPST1	NM_003596.4	MANE Select	c.544A>G	p.Met182Val	missense	Exon 2 of 6	NP_003587.1	O60507

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TPST1	ENST00000304842.6	TSL:1 MANE Select	c.544A>G	p.Met182Val	missense	Exon 2 of 6	ENSP00000302413.5	O60507
	TPST1	ENST00000480281.5	TSL:1	n.189+35447A>G		intron	N/A
	TPST1	ENST00000649664.1		c.544A>G	p.Met182Val	missense	Exon 3 of 7	ENSP00000497281.1	O60507

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		8.0
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
Vest4		0.83
MutPred		0.68		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
Mutation Taster		=11/89	disease causing

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

hg19: chr7-65705956;