NM_001365635.2:c.3137C>T

Variant names:

• chr3-56633654-G-A
• rs9835332
• NM_001365635.2:c.3137C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001365635.2(TASOR):​c.3137C>T​(p.Thr1046Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TASOR NM_001365635.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343
• Publications: 84 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044666052).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365635.2. 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
	TASOR	NM_001365635.2	MANE Select	c.3137C>T	p.Thr1046Ile	missense	Exon 18 of 24	NP_001352564.1	Q9UK61-1
	TASOR	NM_001365636.2		c.3014C>T	p.Thr1005Ile	missense	Exon 18 of 24	NP_001352565.1
	TASOR	NM_001363940.1		c.2954C>T	p.Thr985Ile	missense	Exon 17 of 23	NP_001350869.1	Q9UK61-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TASOR	ENST00000683822.1	MANE Select	c.3137C>T	p.Thr1046Ile	missense	Exon 18 of 24	ENSP00000508241.1	Q9UK61-1
	TASOR	ENST00000355628.9	TSL:1	c.2954C>T	p.Thr985Ile	missense	Exon 17 of 23	ENSP00000347845.5	Q9UK61-4
	TASOR	ENST00000431842.6	TSL:1	c.1826C>T	p.Thr609Ile	missense	Exon 11 of 17	ENSP00000399410.2	Q9UK61-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1461726 Hom.: 0 Cov.: 47 AF XY: 0.00 AC XY: 0 AN XY: 727176

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111958

Other (OTH) AF: 0.00 AC: 0 AN: 60388

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.34
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.025
Sift	Benign	0.10	T
Sift4G	Benign	0.19	T
Polyphen		0.22	B
Vest4		0.087
MutPred		0.52		Gain of glycosylation at T1049 (P = 0.0197)
MVP		0.068
MPC		0.32
ClinPred		0.072	T
GERP RS		0.79
gMVP		0.12
Mutation Taster		=100/0	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: rs9835332; hg19: chr3-56667682;