chrX-13662545-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001297563.2(TCEANC):​c.37C>T​(p.Leu13Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L13V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: TCEANC NM_001297563.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: XL Classification: LIMITED Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.39714155).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297563.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEANC	NM_001297563.2	MANE Select	c.37C>T	p.Leu13Phe	missense	Exon 5 of 5	NP_001284492.1	Q8N8B7-1
	TCEANC	NM_152634.4		c.127C>T	p.Leu43Phe	missense	Exon 4 of 4	NP_689847.2
	TCEANC	NM_001297564.2		c.37C>T	p.Leu13Phe	missense	Exon 3 of 3	NP_001284493.1	Q8N8B7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEANC	ENST00000696128.1	MANE Select	c.37C>T	p.Leu13Phe	missense	Exon 5 of 5	ENSP00000512421.1	Q8N8B7-1
	TCEANC	ENST00000544987.3	TSL:5	c.127C>T	p.Leu43Phe	missense	Exon 4 of 4	ENSP00000440038.2	Q8N8B7-2
	TCEANC	ENST00000380600.2	TSL:3	c.37C>T	p.Leu13Phe	missense	Exon 3 of 3	ENSP00000369974.1	Q8N8B7-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1097690 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1 AN XY: 363140

African (AFR) AF: 0.00 AC: 0 AN: 26386

American (AMR) AF: 0.00 AC: 0 AN: 35143

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19365

East Asian (EAS) AF: 0.00 AC: 0 AN: 30201

South Asian (SAS) AF: 0.00 AC: 0 AN: 53997

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40518

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00000238 AC: 2 AN: 841876

Other (OTH) AF: 0.00 AC: 0 AN: 46068

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.020	T
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.72	T
M_CAP	Pathogenic	0.49	D
MetaRNN	Benign	0.40	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.3
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.15
Sift	Benign	0.15	T
Sift4G	Benign	0.23	T
Polyphen		0.84	P
Vest4		0.12
MutPred		0.69		Gain of catalytic residue at L13 (P = 0.0457)
MVP		0.47
ClinPred		0.83	D
GERP RS		3.1
Varity_R		0.080
gMVP		0.058
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs936231869; hg19: chrX-13680664;