10-5730742-C-T

Position:

• chr10-5730742-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001321783.2(TASOR2):​c.743C>T​(p.Pro248Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TASOR2 NM_001321783.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.860

Genes affected

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

TASOR2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14577669).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TASOR2	NM_001321783.2	c.743C>T	p.Pro248Leu	missense_variant	12/22	ENST00000695737.1	NP_001308712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TASOR2	ENST00000695737.1	c.743C>T	p.Pro248Leu	missense_variant	12/22		NM_001321783.2	ENSP00000512130.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 07, 2023

The c.743C>T (p.P248L) alteration is located in exon 11 (coding exon 8) of the FAM208B gene. This alteration results from a C to T substitution at nucleotide position 743, causing the proline (P) at amino acid position 248 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.028	T;.
Eigen	Benign	0.011
Eigen_PC	Benign	0.049
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-2.7	D;.
REVEL	Benign	0.083
Sift	Benign	0.087	T;.
Sift4G	Uncertain	0.058	T;.
Polyphen		0.65	P;.
Vest4		0.32
MutPred		0.28		Loss of catalytic residue at P247 (P = 0.0135);.;
MVP		0.17
MPC		0.050
ClinPred		0.28	T
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.049
gMVP		0.31

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-5772705;