rs536545317

Variant names:

• chr3-56633240-C-T
• rs536545317
• NM_001365635.2:c.3551G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001365635.2(TASOR):​c.3551G>A​(p.Arg1184Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1184W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: TASOR NM_001365635.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.02
• Publications: 2 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018590748).

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.3551G>A	p.Arg1184Gln	missense	Exon 18 of 24	NP_001352564.1	Q9UK61-1
	TASOR	NM_001365636.2		c.3428G>A	p.Arg1143Gln	missense	Exon 18 of 24	NP_001352565.1
	TASOR	NM_001363940.1		c.3368G>A	p.Arg1123Gln	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.3551G>A	p.Arg1184Gln	missense	Exon 18 of 24	ENSP00000508241.1	Q9UK61-1
	TASOR	ENST00000355628.9	TSL:1	c.3368G>A	p.Arg1123Gln	missense	Exon 17 of 23	ENSP00000347845.5	Q9UK61-4
	TASOR	ENST00000431842.6	TSL:1	c.2240G>A	p.Arg747Gln	missense	Exon 11 of 17	ENSP00000399410.2	Q9UK61-2

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152130 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251298 AF XY: 0.0000294

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000164 AC: 24 AN: 1461828 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14 AN XY: 727204

African (AFR) AF: 0.000329 AC: 11 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111992

Other (OTH) AF: 0.0000497 AC: 3 AN: 60394

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152248 Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12 AN XY: 74422

African (AFR) AF: 0.000529 AC: 22 AN: 41554

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68030

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000128 Hom.: 0

Bravo AF: 0.000140

ExAC AF: 0.0000659 AC: 8

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.2
DANN	Benign	0.70
DEOGEN2	Benign	0.0063	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-0.93	T
PhyloP100		-1.0
PrimateAI	Benign	0.19	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.037
Sift	Benign	0.37	T
Sift4G	Benign	0.60	T
Polyphen		0.012	B
Vest4		0.080
MutPred		0.22		Loss of glycosylation at P1186 (P = 0.3017)
MVP		0.093
MPC		0.30
ClinPred		0.010	T
GERP RS		-4.3
gMVP		0.10
Mutation Taster		=98/2	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: rs536545317; hg19: chr3-56667268; COSMIC: COSV62929553; COSMIC: COSV62929553;