Genetic Variant NM_003195.6:c.510C>G (chr20-64069814-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_003195.6(TCEA2):c.510C>G(p.Ile170Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,498 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TCEA2
NM_003195.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.714

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEA2	NM_003195.6 link	c.510C>G	p.Ile170Met	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 link	c.510C>G	p.Ile170Met	missense_variant	Exon 6 of 10	1	NM_003195.6	ENSP00000343515.5		Q15560-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461498

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 15, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.510C>G (p.I170M) alteration is located in exon 6 (coding exon 6) of the TCEA2 gene. This alteration results from a C to G substitution at nucleotide position 510, causing the isoleucine (I) at amino acid position 170 to be replaced by a methionine (M). 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

0.16

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.19

.;T;T;T;T;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.35

LIST_S2

Uncertain

0.96

D;D;D;.;D;D

M_CAP

Pathogenic

0.31

MetaRNN

Uncertain

0.60

D;D;D;D;D;D

MetaSVM

Uncertain

-0.10

MutationAssessor

Pathogenic

3.7

.;H;.;.;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-2.3

N;N;N;N;N;N

REVEL

Uncertain

0.46

Sift

Uncertain

0.0030

D;D;D;D;D;D

Sift4G

Uncertain

0.020

D;D;D;D;D;D

Polyphen

0.98, 1.0

.;D;D;.;.;.

Vest4

0.85

MutPred

0.73

.;Gain of phosphorylation at S167 (P = 0.1918);Gain of phosphorylation at S167 (P = 0.1918);.;.;.;

MVP

0.40

MPC

1.7

ClinPred

1.0

GERP RS

-9.0

Varity_R

0.33

gMVP

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over