20-64071907-T-A

Variant names:

• chr20-64071907-T-A
• NM_003195.6:c.857T>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003195.6(TCEA2):​c.857T>A​(p.Phe286Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TCEA2 NM_003195.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.97
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.845

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003195.6. 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
	TCEA2	NM_003195.6	MANE Select	c.857T>A	p.Phe286Tyr	missense	Exon 9 of 10	NP_003186.1	Q15560-1
	TCEA2	NM_198723.2		c.776T>A	p.Phe259Tyr	missense	Exon 10 of 11	NP_942016.1	Q15560-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEA2	ENST00000343484.10	TSL:1 MANE Select	c.857T>A	p.Phe286Tyr	missense	Exon 9 of 10	ENSP00000343515.5	Q15560-1
	TCEA2	ENST00000881796.1		c.905T>A	p.Phe302Tyr	missense	Exon 10 of 11	ENSP00000551855.1
	TCEA2	ENST00000940921.1		c.875T>A	p.Phe292Tyr	missense	Exon 9 of 10	ENSP00000610980.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.015	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.076
Eigen_PC	Benign	-0.080
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.040	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		5.0
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.26
Sift	Benign	0.033	D
Sift4G	Uncertain	0.036	D
Polyphen		0.24	B
Vest4		0.44
MutPred		0.91		Gain of phosphorylation at F286 (P = 0.0884)
MVP		0.33
MPC		0.81
ClinPred		0.97	D
GERP RS		1.5
Varity_R		0.20
gMVP		0.84
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr20-62703260;