rs2041230291

Variant names:

• chr20-13390451-G-C
• rs2041230291
• NM_017714.3:c.1172C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017714.3(TASP1):​c.1172C>G​(p.Thr391Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000479 in 1,461,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TASP1 NM_017714.3 missense, splice_region
• Scores: Splicing: ADA: 0.0006708
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.73
• Publications: 0 publications found

Genes affected

TASP1 (HGNC:15859): (taspase 1) This gene encodes an endopeptidase that cleaves specific substrates following aspartate residues. The encoded protein undergoes posttranslational autoproteolytic processing to generate alpha and beta subunits, which reassemble into the active alpha2-beta2 heterotetramer. It is required to cleave MLL, a protein required for the maintenance of HOX gene expression, and TFIIA, a basal transcription factor. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

TASP1 Gene-Disease associations (from GenCC):

• Suleiman-El-Hattab syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17222327).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017714.3. 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
	TASP1	NM_017714.3	MANE Select	c.1172C>G	p.Thr391Ser	missense splice_region	Exon 14 of 14	NP_060184.2	Q9H6P5-1
	TASP1	NM_001323603.2		c.866C>G	p.Thr289Ser	missense splice_region	Exon 15 of 15	NP_001310532.1
	TASP1	NM_001323604.2		c.866C>G	p.Thr289Ser	missense splice_region	Exon 15 of 15	NP_001310533.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TASP1	ENST00000337743.9	TSL:1 MANE Select	c.1172C>G	p.Thr391Ser	missense splice_region	Exon 14 of 14	ENSP00000338624.4	Q9H6P5-1
	TASP1	ENST00000961261.1		c.1262C>G	p.Thr421Ser	missense splice_region	Exon 14 of 14	ENSP00000631320.1
	TASP1	ENST00000861004.1		c.1172C>G	p.Thr391Ser	missense splice_region	Exon 15 of 15	ENSP00000531063.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461200 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 726896

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111710

Other (OTH) AF: 0.0000166 AC: 1 AN: 60372

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.63
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	21
DANN	Benign	0.86
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.086
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.17	T
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	0.98	L
PhyloP100		4.7
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.23
Sift	Benign	0.66	T
Sift4G	Benign	0.62	T
Polyphen		0.039	B
Vest4		0.34
MutPred		0.45		Loss of sheet (P = 0.0315)
MVP		0.16
MPC		0.48
ClinPred		0.49	T
GERP RS		5.0
Varity_R		0.31
gMVP		0.59
Mutation Taster		=58/42	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00067
dbscSNV1_RF	Benign	0.030
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

dbSNP: rs2041230291; hg19: chr20-13371098;