20-64069486-C-T

Variant names:

• chr20-64069486-C-T
• rs373957561
• NM_003195.6:c.455C>T

Variant summary

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

The NM_003195.6(TCEA2):​c.455C>T​(p.Thr152Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000477 in 1,612,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: TCEA2 NM_003195.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.62
• Publications: 3 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33327466).

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.455C>T	p.Thr152Met	missense	Exon 5 of 10	NP_003186.1	Q15560-1
	TCEA2	NM_198723.2		c.374C>T	p.Thr125Met	missense	Exon 6 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.455C>T	p.Thr152Met	missense	Exon 5 of 10	ENSP00000343515.5	Q15560-1
	TCEA2	ENST00000487164.5	TSL:1	n.610C>T		non_coding_transcript_exon	Exon 5 of 6
	TCEA2	ENST00000881796.1		c.506C>T	p.Thr169Met	missense	Exon 6 of 11	ENSP00000551855.1

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152222 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 247536 AF XY: 0.00000744

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000270

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000493 AC: 72 AN: 1460404 Hom.: 0 Cov.: 32 AF XY: 0.0000385 AC XY: 28 AN XY: 726546

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5724

European-Non Finnish (NFE) AF: 0.0000585 AC: 65 AN: 1111720

Other (OTH) AF: 0.0000828 AC: 5 AN: 60356

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152222 Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3 AN XY: 74372

African (AFR) AF: 0.0000483 AC: 2 AN: 41450

American (AMR) AF: 0.0000654 AC: 1 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000247 AC: 3

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

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	Benign	0.074
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.072	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.62	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		4.6
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.13
Sift	Benign	0.074	T
Sift4G	Benign	0.19	T
Polyphen		0.82	P
Vest4		0.32
MVP		0.77
MPC		1.7
ClinPred		0.81	D
GERP RS		4.5
Varity_R		0.071
gMVP		0.34
Mutation Taster		=48/52	disease causing

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: rs373957561; hg19: chr20-62700839; COSMIC: COSV58658435; COSMIC: COSV58658435;