X-13662720-T-G

Variant names:

• chrX-13662720-T-G
• rs754192147
• NM_001297563.2:c.212T>G

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001297563.2(TCEANC):​c.212T>G​(p.Leu71Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000638 in 1,098,021 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000064 (0 hom. 0 hem.)
• Consequence: TCEANC NM_001297563.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.93

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.848

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEANC	NM_001297563.2	c.212T>G	p.Leu71Trp	missense_variant	Exon 5 of 5	ENST00000696128.1	NP_001284492.1
TCEANC	NM_152634.4	c.302T>G	p.Leu101Trp	missense_variant	Exon 4 of 4		NP_689847.2
TCEANC	NM_001297564.2	c.212T>G	p.Leu71Trp	missense_variant	Exon 3 of 3		NP_001284493.1
TCEANC	XM_017029316.2	c.302T>G	p.Leu101Trp	missense_variant	Exon 4 of 4		XP_016884805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEANC	ENST00000696128.1	c.212T>G	p.Leu71Trp	missense_variant	Exon 5 of 5		NM_001297563.2	ENSP00000512421.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.0000166 AC: 3 AN: 180928 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 66968

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000223

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: 0.00000638 AC: 7 AN: 1098021 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363451

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000232

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.: 23

ExAC AF: 0.00000828 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.302T>G (p.L101W) alteration is located in exon 4 (coding exon 2) of the TCEANC gene. This alteration results from a T to G substitution at nucleotide position 302, causing the leucine (L) at amino acid position 101 to be replaced by a tryptophan (W). 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	Uncertain	0.50
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Benign	0.96
DEOGEN2	Benign	0.29	T;.
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T;T
M_CAP	Pathogenic	0.45	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-5.3	D;.
REVEL	Uncertain	0.52
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.77
MutPred		0.61		Gain of methylation at K76 (P = 0.0657);.;
MVP		0.66
ClinPred		0.81	D
GERP RS		5.3
Varity_R		0.79
gMVP		0.79

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

Other links and lift over

dbSNP: rs754192147; hg19: chrX-13680839;