3-56633654-G-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365635.2(TASOR):​c.3137C>G​(p.Thr1046Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 1,613,588 control chromosomes in the GnomAD database, including 238,541 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 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: 𝑓 0.62 (31577 hom., cov: 32)
  • Exomes 𝑓: 0.52 (206964 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.6915053E-7).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

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>G	p.Thr1046Arg	missense	Exon 18 of 24	NP_001352564.1	Q9UK61-1
	TASOR	NM_001365636.2		c.3014C>G	p.Thr1005Arg	missense	Exon 18 of 24	NP_001352565.1
	TASOR	NM_001363940.1		c.2954C>G	p.Thr985Arg	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>G	p.Thr1046Arg	missense	Exon 18 of 24	ENSP00000508241.1	Q9UK61-1
	TASOR	ENST00000355628.9	TSL:1	c.2954C>G	p.Thr985Arg	missense	Exon 17 of 23	ENSP00000347845.5	Q9UK61-4
	TASOR	ENST00000431842.6	TSL:1	c.1826C>G	p.Thr609Arg	missense	Exon 11 of 17	ENSP00000399410.2	Q9UK61-2

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93739 AN: 152006 Hom.: 31506 Cov.: 32

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.770

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.625

GnomAD2 exomes AF: 0.606 AC: 152150 AN: 251110 AF XY: 0.598

Gnomad AFR exome AF: 0.855

Gnomad AMR exome AF: 0.776

Gnomad ASJ exome AF: 0.439

Gnomad EAS exome AF: 0.964

Gnomad FIN exome AF: 0.488

Gnomad NFE exome AF: 0.461

Gnomad OTH exome AF: 0.545

GnomAD4 exome AF: 0.517 AC: 755555 AN: 1461464 Hom.: 206964 Cov.: 47 AF XY: 0.520 AC XY: 378278 AN XY: 727038

African (AFR) AF: 0.858 AC: 28726 AN: 33464

American (AMR) AF: 0.763 AC: 34096 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 11475 AN: 26124

East Asian (EAS) AF: 0.932 AC: 36999 AN: 39700

South Asian (SAS) AF: 0.748 AC: 64526 AN: 86240

European-Finnish (FIN) AF: 0.484 AC: 25797 AN: 53324

Middle Eastern (MID) AF: 0.517 AC: 2982 AN: 5764

European-Non Finnish (NFE) AF: 0.465 AC: 517289 AN: 1111780

Other (OTH) AF: 0.558 AC: 33665 AN: 60376

GnomAD4 genome AF: 0.617 AC: 93872 AN: 152124 Hom.: 31577 Cov.: 32 AF XY: 0.623 AC XY: 46353 AN XY: 74374

African (AFR) AF: 0.846 AC: 35136 AN: 41522

American (AMR) AF: 0.680 AC: 10397 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1458 AN: 3470

East Asian (EAS) AF: 0.956 AC: 4955 AN: 5184

South Asian (SAS) AF: 0.770 AC: 3709 AN: 4818

European-Finnish (FIN) AF: 0.495 AC: 5226 AN: 10564

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30993 AN: 67962

Other (OTH) AF: 0.629 AC: 1328 AN: 2112

Alfa AF: 0.497 Hom.: 15179

Bravo AF: 0.642

TwinsUK AF: 0.461 AC: 1708

ALSPAC AF: 0.449 AC: 1731

ESP6500AA AF: 0.846 AC: 3727

ESP6500EA AF: 0.461 AC: 3967

ExAC AF: 0.603 AC: 73207

Asia WGS AF: 0.857 AC: 2975 AN: 3478

EpiCase AF: 0.455

EpiControl AF: 0.464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.043
BayesDel_addAF	Benign	-0.84	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.21
DEOGEN2	Benign	0.0024	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.071	T
MetaRNN	Benign	5.7e-7	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.34
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.54	N
REVEL	Benign	0.019
Sift	Benign	1.0	T
Sift4G	Benign	0.63	T
Polyphen		0.0	B
Vest4		0.051
MPC		0.30
ClinPred		0.00030	T
GERP RS		0.79
gMVP		0.12
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV62928966; COSMIC: COSV62928966;