Genetic Variant TCEANC:p.His238Tyr (chrX-13663220-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_001297563.2(TCEANC):c.712C>T(p.His238Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000291 in 1,203,981 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 2 hem., cov: 23)

Exomes 𝑓: 0.000020 ( 0 hom. 6 hem. )

Consequence

TCEANC
NM_001297563.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.58

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 GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEANC	NM_001297563.2 link	c.712C>T	p.His238Tyr	missense_variant	Exon 5 of 5	ENST00000696128.1	NP_001284492.1	Q8N8B7-1A8K5F6
TCEANC	NM_152634.4 link	c.802C>T	p.His268Tyr	missense_variant	Exon 4 of 4		NP_689847.2	B4DG85
TCEANC	NM_001297564.2 link	c.712C>T	p.His238Tyr	missense_variant	Exon 3 of 3		NP_001284493.1	Q8N8B7-1
TCEANC	XM_017029316.2 link	c.802C>T	p.His268Tyr	missense_variant	Exon 4 of 4		XP_016884805.1	Q8N8B7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEANC	ENST00000696128.1 link	c.712C>T	p.His238Tyr	missense_variant	Exon 5 of 5		NM_001297563.2	ENSP00000512421.1		Q8N8B7-1

Frequencies

GnomAD3 genomes

AF:

0.000116

AC:

AN:

112087

Hom.:

Cov.:

AF XY:

0.0000584

AC XY:

AN XY:

34251

show subpopulations

Gnomad AFR

AF:

0.0000974

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000853

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000278

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:

0.0000301

AC:

AN:

165897

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

54321

show subpopulations

Gnomad AFR exome

AF:

0.0000880

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000797

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000719

GnomAD4 exome

AF:

0.0000201

AC:

AN:

1091843

Hom.:

Cov.:

AF XY:

0.0000168

AC XY:

AN XY:

358033

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000133

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.000349

GnomAD4 genome

AF:

0.000116

AC:

AN:

112138

Hom.:

Cov.:

AF XY:

0.0000583

AC XY:

AN XY:

34312

show subpopulations

Gnomad4 AFR

AF:

0.0000972

Gnomad4 AMR

AF:

0.000852

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000279

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000321

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000332

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 06, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.802C>T (p.H268Y) alteration is located in exon 4 (coding exon 2) of the TCEANC gene. This alteration results from a C to T substitution at nucleotide position 802, causing the histidine (H) at amino acid position 268 to be replaced by a tyrosine (Y). 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

-0.31

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

T;.

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.81

T;T

M_CAP

Pathogenic

0.53

MetaRNN

Uncertain

0.52

D;D

MetaSVM

Benign

-0.54

MutationAssessor

Pathogenic

3.0

M;.

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-3.9

D;.

REVEL

Benign

0.22

Sift

Uncertain

0.0030

D;.

Sift4G

Uncertain

0.0070

D;D

Polyphen

1.0

D;D

Vest4

0.41

MVP

0.57

ClinPred

0.53

GERP RS

5.6

Varity_R

0.94

gMVP

0.34

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