10-5724477-A-C

Variant names:

• chr10-5724477-A-C
• rs373569620
• NM_001321783.2:c.295A>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001321783.2(TASOR2):​c.295A>C​(p.Asn99His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000216 in 1,388,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. N99D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000022 (0 hom.)
• Consequence: TASOR2 NM_001321783.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.07
• Publications: 0 publications found

Genes affected

TASOR2 (HGNC:23484): (transcription activation suppressor family member 2) Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000226647 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.323439).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321783.2. 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
	TASOR2	NM_001321783.2	MANE Select	c.295A>C	p.Asn99His	missense	Exon 9 of 22	NP_001308712.2	Q5VWN6-1
	TASOR2	NM_001387328.1		c.940A>C	p.Asn314His	missense	Exon 11 of 24	NP_001374257.1	A0A2R8YH03
	TASOR2	NM_001321784.2		c.295A>C	p.Asn99His	missense	Exon 9 of 22	NP_001308713.2	Q5VWN6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TASOR2	ENST00000695737.1	MANE Select	c.295A>C	p.Asn99His	missense	Exon 9 of 22	ENSP00000512130.1	Q5VWN6-1
	TASOR2	ENST00000328090.9	TSL:1	c.295A>C	p.Asn99His	missense	Exon 8 of 21	ENSP00000328426.5	Q5VWN6-1
	TASOR2	ENST00000699051.1		c.1078A>C	p.Asn360His	missense	Exon 12 of 25	ENSP00000514102.1	A0A8V8TMN1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000216 AC: 3 AN: 1388658 Hom.: 0 Cov.: 27 AF XY: 0.00000145 AC XY: 1 AN XY: 689290

African (AFR) AF: 0.00 AC: 0 AN: 29588

American (AMR) AF: 0.00 AC: 0 AN: 33220

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24482

East Asian (EAS) AF: 0.00 AC: 0 AN: 34362

South Asian (SAS) AF: 0.00 AC: 0 AN: 73374

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5548

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1080586

Other (OTH) AF: 0.00 AC: 0 AN: 56914

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.1
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.57		Loss of sheet (P = 0.0817)
MVP		0.40
MPC		0.31
ClinPred		0.97	D
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.32
gMVP		0.33
Mutation Taster		=90/10	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: rs373569620; hg19: chr10-5766440;