chr3-56624574-A-T

Variant names:

• chr3-56624574-A-T
• NM_001365635.2:c.4388T>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001365635.2(TASOR):​c.4388T>A​(p.Met1463Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TASOR NM_001365635.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.54

Genes affected

TASOR (HGNC:30314): (transcription activation suppressor) Enables chromatin binding activity. Involved in negative regulation of single stranded viral RNA replication via double stranded DNA intermediate; protein localization to heterochromatin; and regulation of gene expression. Located in heterochromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.771

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TASOR	NM_001365635.2	c.4388T>A	p.Met1463Lys	missense_variant	Exon 23 of 24	ENST00000683822.1	NP_001352564.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TASOR	ENST00000683822.1	c.4388T>A	p.Met1463Lys	missense_variant	Exon 23 of 24		NM_001365635.2	ENSP00000508241.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461672 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727138

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.23	.;.;.;T
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	D;D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.77	D;D;D;D
MetaSVM	Benign	-1.2	T
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-4.2	D;D;D;.
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D;D;.;.
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		0.98	D;B;B;.
Vest4		0.92
MutPred		0.59		.;Gain of ubiquitination at M1463 (P = 0.0247);.;.;
MVP		0.28
MPC		0.96
ClinPred		0.98	D
GERP RS		5.4
gMVP		0.87

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: chr3-56658602;