20-64069776-G-A

Variant names:

• chr20-64069776-G-A
• rs771619709
• NM_003195.6:c.472G>A

Variant summary

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

The NM_003195.6(TCEA2):​c.472G>A​(p.Ala158Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,459,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 34)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TCEA2 NM_003195.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.61

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=0.17035627).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEA2	NM_003195.6	c.472G>A	p.Ala158Thr	missense_variant	Exon 6 of 10	ENST00000343484.10	NP_003186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEA2	ENST00000343484.10	c.472G>A	p.Ala158Thr	missense_variant	Exon 6 of 10	1	NM_003195.6	ENSP00000343515.5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000798 AC: 2 AN: 250598 Hom.: 0 AF XY: 0.0000148 AC XY: 2 AN XY: 135412

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1459884 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 725890

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000672

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Bravo AF: 0.0000113

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.472G>A (p.A158T) alteration is located in exon 6 (coding exon 6) of the TCEA2 gene. This alteration results from a G to A substitution at nucleotide position 472, causing the alanine (A) at amino acid position 158 to be replaced by a threonine (T). 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	0.070
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.057	.;T;T;T;T;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.75	D
LIST_S2	Uncertain	0.92	D;D;D;.;D;D
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.17	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	.;L;.;.;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.2	N;N;N;N;N;N
REVEL	Benign	0.030
Sift	Benign	0.51	T;T;T;T;T;T
Sift4G	Benign	0.56	T;T;T;T;T;T
Polyphen		0.018, 0.91	.;B;P;.;.;.
Vest4		0.36
MutPred		0.45		.;Gain of glycosylation at A158 (P = 0.0625);Gain of glycosylation at A158 (P = 0.0625);.;.;.;
MVP		0.62
MPC		0.79
ClinPred		0.34	T
GERP RS		3.6
Varity_R		0.078
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs771619709; hg19: chr20-62701129;