20-64070568-C-T

Variant names:

• chr20-64070568-C-T
• rs1185243973
• NM_003195.6:c.752C>T

Variant summary

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

The NM_003195.6(TCEA2):​c.752C>T​(p.Thr251Ile) 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. 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. T251A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 34)
• Consequence: TCEA2 NM_003195.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

Genes affected

TCEA2 (HGNC:11614): (transcription elongation factor A2) The protein encoded by this gene is found in the nucleus, where it functions as an SII class transcription elongation factor. Elongation factors in this class are responsible for releasing RNA polymerase II ternary complexes from transcriptional arrest at template-encoded arresting sites. The encoded protein has been shown to interact with general transcription factor IIB, a basal transcription factor. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

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=0.21210149).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEA2	NM_003195.6	c.752C>T	p.Thr251Ile	missense_variant	Exon 8 of 10	ENST00000343484.10	NP_003186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEA2	ENST00000343484.10	c.752C>T	p.Thr251Ile	missense_variant	Exon 8 of 10	1	NM_003195.6	ENSP00000343515.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.046	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	.;T;T;T;T
Eigen	Benign	-0.086
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.29	N
LIST_S2	Uncertain	0.97	D;D;.;D;D
M_CAP	Benign	0.084	D
MetaRNN	Benign	0.21	T;T;T;T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.7	.;M;.;.;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.8	D;D;D;D;D
REVEL	Benign	0.085
Sift	Benign	0.069	T;T;T;T;T
Sift4G	Benign	0.096	T;T;T;T;T
Polyphen		0.84	.;P;.;.;.
Vest4		0.33
MutPred		0.28		.;Loss of disorder (P = 0.0591);.;.;.;
MVP		0.48
MPC		0.78
ClinPred		0.96	D
GERP RS		3.5
Varity_R		0.23
gMVP		0.48

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

LitVar

Other links and lift over

dbSNP: rs1185243973; hg19: chr20-62701921;