dbSNP rs372369033: TCEA2:p.Pro130Gln (chr20-64069420-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_003195.6(TCEA2):c.389C>A(p.Pro130Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,460,542 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P130L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

TCEA2
NM_003195.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.15

Publications

0 publications found

Variant links:

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]

TCEA2 links:

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ACMG classification

Classification was made for transcript

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

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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.389C>A	p.Pro130Gln	missense	Exon 5 of 10	NP_003186.1	Q15560-1
	TCEA2	NM_198723.2		c.308C>A	p.Pro103Gln	missense	Exon 6 of 11	NP_942016.1	Q15560-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCEA2	ENST00000343484.10	TSL:1 MANE Select	c.389C>A	p.Pro130Gln	missense	Exon 5 of 10	ENSP00000343515.5	Q15560-1
TCEA2	ENST00000487164.5	TSL:1	n.544C>A		non_coding_transcript_exon	Exon 5 of 6
TCEA2	ENST00000881796.1		c.440C>A	p.Pro147Gln	missense	Exon 6 of 11	ENSP00000551855.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1460542

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

726568

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26094

East Asian (EAS)

AF:

0.00

AC:

AN:

39664

South Asian (SAS)

AF:

0.00

AC:

AN:

86050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52800

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111752

Other (OTH)

AF:

0.00

AC:

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Uncertain

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.087

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.84

M_CAP

Benign

0.060

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

1.1

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.079

Sift

Benign

0.26

Sift4G

Benign

0.17

Polyphen

0.0070

Vest4

0.26

MutPred

0.21

Gain of solvent accessibility (P = 0.1045)

MVP

0.51

MPC

0.84

ClinPred

0.43

GERP RS

3.7

Varity_R

0.058

gMVP

0.40

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.87

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.87

Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over