X-13662545-C-G

Variant names:

• chrX-13662545-C-G
• rs936231869
• NM_001297563.2:c.37C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001297563.2(TCEANC):​c.37C>G​(p.Leu13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000729 in 1,097,690 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000073 (0 hom. 1 hem.)
• Consequence: TCEANC NM_001297563.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21463767).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEANC	NM_001297563.2	c.37C>G	p.Leu13Val	missense_variant	Exon 5 of 5	ENST00000696128.1	NP_001284492.1
TCEANC	NM_152634.4	c.127C>G	p.Leu43Val	missense_variant	Exon 4 of 4		NP_689847.2
TCEANC	NM_001297564.2	c.37C>G	p.Leu13Val	missense_variant	Exon 3 of 3		NP_001284493.1
TCEANC	XM_017029316.2	c.127C>G	p.Leu43Val	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.37C>G	p.Leu13Val	missense_variant	Exon 5 of 5		NM_001297563.2	ENSP00000512421.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000729 AC: 8 AN: 1097690 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363140

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: 0.00000831

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 23

Alfa AF: 0.000187 Hom.: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.127C>G (p.L43V) 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 127, causing the leucine (L) at amino acid position 43 to be replaced by a valine (V). 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	0.070
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	10
DANN	Benign	0.85
DEOGEN2	Benign	0.0091	T;.
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.72	T;T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.0	N;D
REVEL	Benign	0.082
Sift	Benign	0.32	T;D
Sift4G	Benign	0.45	T;T
Polyphen		0.44	B;P
Vest4		0.11
MutPred		0.66		Gain of MoRF binding (P = 0.1255);.;
MVP		0.61
ClinPred		0.23	T
GERP RS		3.1
Varity_R		0.069
gMVP		0.063

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: rs936231869; hg19: chrX-13680664;