NM_017714.3:c.765G>A

Variant names:

• chr20-13534052-C-T
• rs145022707
• NM_017714.3:c.765G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6 BP7 BS1 BS2

The NM_017714.3(TASP1):​c.765G>A​(p.Leu255Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00372 in 1,613,410 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0032 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (35 hom.)
• Consequence: TASP1 NM_017714.3 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.04
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 20-13534052-C-T is Benign according to our data. Variant chr20-13534052-C-T is described in ClinVar as Benign. ClinVar VariationId is 3033137.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=1.04 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.00377 (5502/1461220) while in subpopulation AMR AF = 0.0195 (873/44662). AF 95% confidence interval is 0.0185. There are 35 homozygotes in GnomAdExome4. There are 2730 alleles in the male GnomAdExome4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.765G>A	p.Leu255Leu	synonymous	Exon 9 of 14	NP_060184.2	Q9H6P5-1
	TASP1	NM_001323603.2		c.459G>A	p.Leu153Leu	synonymous	Exon 10 of 15	NP_001310532.1
	TASP1	NM_001323604.2		c.459G>A	p.Leu153Leu	synonymous	Exon 10 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.765G>A	p.Leu255Leu	synonymous	Exon 9 of 14	ENSP00000338624.4	Q9H6P5-1
	TASP1	ENST00000961261.1		c.765G>A	p.Leu255Leu	synonymous	Exon 8 of 14	ENSP00000631320.1
	TASP1	ENST00000861004.1		c.765G>A	p.Leu255Leu	synonymous	Exon 10 of 15	ENSP00000531063.1

Frequencies

GnomAD3 genomes AF: 0.00324 AC: 492 AN: 152072 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00675

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.0118

Gnomad SAS AF: 0.00332

Gnomad FIN AF: 0.00519

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00343

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00607 AC: 1522 AN: 250782 AF XY: 0.00535

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0208

Gnomad ASJ exome AF: 0.000597

Gnomad EAS exome AF: 0.00986

Gnomad FIN exome AF: 0.00619

Gnomad NFE exome AF: 0.00332

Gnomad OTH exome AF: 0.00589

GnomAD4 exome AF: 0.00377 AC: 5502 AN: 1461220 Hom.: 35 Cov.: 30 AF XY: 0.00376 AC XY: 2730 AN XY: 726918

African (AFR) AF: 0.000449 AC: 15 AN: 33440

American (AMR) AF: 0.0195 AC: 873 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.000766 AC: 20 AN: 26118

East Asian (EAS) AF: 0.00799 AC: 317 AN: 39668

South Asian (SAS) AF: 0.00231 AC: 199 AN: 86212

European-Finnish (FIN) AF: 0.00627 AC: 335 AN: 53408

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5760

European-Non Finnish (NFE) AF: 0.00317 AC: 3519 AN: 1111594

Other (OTH) AF: 0.00360 AC: 217 AN: 60358

GnomAD4 genome AF: 0.00324 AC: 493 AN: 152190 Hom.: 2 Cov.: 32 AF XY: 0.00348 AC XY: 259 AN XY: 74396

African (AFR) AF: 0.000289 AC: 12 AN: 41530

American (AMR) AF: 0.00694 AC: 106 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.0116 AC: 60 AN: 5168

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4816

European-Finnish (FIN) AF: 0.00519 AC: 55 AN: 10596

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00343 AC: 233 AN: 68012

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00335 Hom.: 0

Bravo AF: 0.00351

Asia WGS AF: 0.0170 AC: 58 AN: 3478

EpiCase AF: 0.00338

EpiControl AF: 0.00220

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	TASP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism

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

dbSNP: rs145022707; hg19: chr20-13514699; COSMIC: COSV107427965;