Variant X-13663254-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001297563.2(TCEANC):c.746C>G(p.Ser249Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000416 in 1,201,928 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.0000037 ( 0 hom. 2 hem. )

Consequence

TCEANC
NM_001297563.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.26

Variant links:

Genes affected

TCEANC (HGNC:28277): (transcription elongation factor A N-terminal and central domain containing) Predicted to be involved in transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TCEANC links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCEANC	NM_001297563.2 link	c.746C>G	p.Ser249Cys	missense_variant	5/5	ENST00000696128.1	NP_001284492.1	Q8N8B7-1A8K5F6
TCEANC	NM_152634.4 link	c.836C>G	p.Ser279Cys	missense_variant	4/4		NP_689847.2	B4DG85
TCEANC	NM_001297564.2 link	c.746C>G	p.Ser249Cys	missense_variant	3/3		NP_001284493.1	Q8N8B7-1
TCEANC	XM_017029316.2 link	c.836C>G	p.Ser279Cys	missense_variant	4/4		XP_016884805.1	Q8N8B7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCEANC	ENST00000696128.1 link	c.746C>G	p.Ser249Cys	missense_variant	5/5		NM_001297563.2	ENSP00000512421.1		Q8N8B7-1

Frequencies

GnomAD3 genomes

AF:

0.00000890

AC:

AN:

112355

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34511

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000944

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000185

AC:

AN:

162280

Hom.:

AF XY:

0.0000193

AC XY:

AN XY:

51890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000118

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:

0.00000367

AC:

AN:

1089573

Hom.:

Cov.:

AF XY:

0.00000561

AC XY:

AN XY:

356603

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000118

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

AF:

0.00000890

AC:

AN:

112355

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34511

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000944

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 12, 2022

The c.836C>G (p.S279C) alteration is located in exon 4 (coding exon 2) of the TCEANC gene. This alteration results from a C to G substitution at nucleotide position 836, causing the serine (S) at amino acid position 279 to be replaced by a cysteine (C). 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

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

T;.

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.82

T;T

M_CAP

Pathogenic

0.58

MetaRNN

Uncertain

0.63

D;D

MetaSVM

Uncertain

-0.16

MutationAssessor

Pathogenic

3.6

H;.

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.8

D;.

REVEL

Uncertain

0.30

Sift

Uncertain

0.0020

D;.

Sift4G

Uncertain

0.0070

D;D

Polyphen

1.0

D;D

Vest4

0.42

MutPred

0.48

Loss of disorder (P = 0.0283);.;

MVP

0.34

ClinPred

0.76

GERP RS

5.6

Varity_R

0.80

gMVP

0.35

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over