3-56624453-G-C

Variant names:

• chr3-56624453-G-C
• rs2291499
• NM_001365635.2:c.4483+26C>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.4483+26C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,600,214 control chromosomes in the GnomAD database, including 65,753 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (8076 hom., cov: 32)
  • Exomes 𝑓: 0.28 (57677 hom.)
• Consequence: TASOR NM_001365635.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.437
• Publications: 9 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 (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TASOR	NM_001365635.2	MANE Select	c.4483+26C>G		intron	N/A	NP_001352564.1
	TASOR	NM_001365636.2		c.4360+26C>G		intron	N/A	NP_001352565.1
	TASOR	NM_001363940.1		c.4300+26C>G		intron	N/A	NP_001350869.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TASOR	ENST00000683822.1	MANE Select	c.4483+26C>G		intron	N/A	ENSP00000508241.1
	TASOR	ENST00000355628.9	TSL:1	c.4300+26C>G		intron	N/A	ENSP00000347845.5
	TASOR	ENST00000431842.6	TSL:1	c.3172+26C>G		intron	N/A	ENSP00000399410.2

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48169 AN: 151832 Hom.: 8072 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.344

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.163

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.314

GnomAD2 exomes AF: 0.316 AC: 76569 AN: 241960 AF XY: 0.303

Gnomad AFR exome AF: 0.374

Gnomad AMR exome AF: 0.506

Gnomad ASJ exome AF: 0.233

Gnomad EAS exome AF: 0.480

Gnomad FIN exome AF: 0.305

Gnomad NFE exome AF: 0.258

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.276 AC: 399088 AN: 1448264 Hom.: 57677 Cov.: 31 AF XY: 0.273 AC XY: 196208 AN XY: 720022

African (AFR) AF: 0.365 AC: 11917 AN: 32666

American (AMR) AF: 0.495 AC: 20694 AN: 41774

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 5851 AN: 25636

East Asian (EAS) AF: 0.465 AC: 18379 AN: 39556

South Asian (SAS) AF: 0.237 AC: 20033 AN: 84510

European-Finnish (FIN) AF: 0.298 AC: 15853 AN: 53154

Middle Eastern (MID) AF: 0.156 AC: 887 AN: 5674

European-Non Finnish (NFE) AF: 0.261 AC: 288385 AN: 1105446

Other (OTH) AF: 0.286 AC: 17089 AN: 59848

GnomAD4 genome AF: 0.317 AC: 48209 AN: 151950 Hom.: 8076 Cov.: 32 AF XY: 0.321 AC XY: 23868 AN XY: 74262

African (AFR) AF: 0.372 AC: 15412 AN: 41438

American (AMR) AF: 0.436 AC: 6660 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3470

East Asian (EAS) AF: 0.485 AC: 2502 AN: 5154

South Asian (SAS) AF: 0.239 AC: 1153 AN: 4824

European-Finnish (FIN) AF: 0.311 AC: 3278 AN: 10528

Middle Eastern (MID) AF: 0.176 AC: 51 AN: 290

European-Non Finnish (NFE) AF: 0.257 AC: 17440 AN: 67948

Other (OTH) AF: 0.314 AC: 663 AN: 2110

Alfa AF: 0.197 Hom.: 613

Bravo AF: 0.332

Asia WGS AF: 0.361 AC: 1257 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	17
DANN	Benign	0.68
PhyloP100		0.44
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: rs2291499; hg19: chr3-56658481; COSMIC: COSV58302205; COSMIC: COSV58302205;