chr20-13483235-T-G

Variant names:

• chr20-13483235-T-G
• NM_017714.3:c.977A>C

Variant summary

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

The NM_017714.3(TASP1):​c.977A>C​(p.Lys326Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000701 in 1,426,664 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: 7.0e-7 (0 hom.)
• Consequence: TASP1 NM_017714.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.39

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]

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 rank	MANE	Protein	UniProt
TASP1	NM_017714.3	c.977A>C	p.Lys326Thr	missense_variant	Exon 11 of 14	ENST00000337743.9	NP_060184.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TASP1	ENST00000337743.9	c.977A>C	p.Lys326Thr	missense_variant	Exon 11 of 14	1	NM_017714.3	ENSP00000338624.4
TASP1	ENST00000455532.5	c.908A>C	p.Lys303Thr	missense_variant	Exon 10 of 10	5		ENSP00000400580.1
TASP1	ENST00000465381.5	n.874A>C		non_coding_transcript_exon_variant	Exon 9 of 10	5
TASP1	ENST00000480436.5	n.1048A>C		non_coding_transcript_exon_variant	Exon 11 of 14	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1426664 Hom.: 0 Cov.: 29 AF XY: 0.00000141 AC XY: 1 AN XY: 708652

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.13e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	D;T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Uncertain	0.099	D
MetaRNN	Uncertain	0.56	D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.9	N;N
REVEL	Pathogenic	0.77
Sift	Uncertain	0.026	D;D
Sift4G	Benign	0.23	T;.
Polyphen		0.85	P;P
Vest4		0.82
MutPred		0.49		Loss of methylation at K326 (P = 0.0045);.;
MVP		0.73
MPC		1.2
ClinPred		0.89	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.67
gMVP		0.82

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: chr20-13463882;