3-56627133-T-G

Variant names:

• chr3-56627133-T-G
• rs199831929
• NM_001365635.2:c.4043A>C

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.4043A>C​(p.Asn1348Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,604 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1348I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TASOR NM_001365635.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 0 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=0.051086187).

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.4043A>C	p.Asn1348Thr	missense	Exon 21 of 24	NP_001352564.1	Q9UK61-1
	TASOR	NM_001365636.2		c.3920A>C	p.Asn1307Thr	missense	Exon 21 of 24	NP_001352565.1
	TASOR	NM_001363940.1		c.3860A>C	p.Asn1287Thr	missense	Exon 20 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.4043A>C	p.Asn1348Thr	missense	Exon 21 of 24	ENSP00000508241.1	Q9UK61-1
	TASOR	ENST00000355628.9	TSL:1	c.3860A>C	p.Asn1287Thr	missense	Exon 20 of 23	ENSP00000347845.5	Q9UK61-4
	TASOR	ENST00000431842.6	TSL:1	c.2732A>C	p.Asn911Thr	missense	Exon 14 of 17	ENSP00000399410.2	Q9UK61-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1449604 Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1 AN XY: 721934

African (AFR) AF: 0.00 AC: 0 AN: 33006

American (AMR) AF: 0.00 AC: 0 AN: 43770

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25926

East Asian (EAS) AF: 0.00 AC: 0 AN: 39512

South Asian (SAS) AF: 0.00 AC: 0 AN: 85344

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1103054

Other (OTH) AF: 0.0000167 AC: 1 AN: 59906

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.14
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.023
Sift	Benign	0.39	T
Sift4G	Benign	0.43	T
Polyphen		0.12	B
Vest4		0.22
MutPred		0.30		Loss of ubiquitination at K1347 (P = 0.0777)
MVP		0.21
MPC		0.29
ClinPred		0.070	T
GERP RS		-4.6
gMVP		0.089
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs199831929; hg19: chr3-56661161; COSMIC: COSV100843413; COSMIC: COSV100843413;