chrX-13662777-C-T

Variant names:

• chrX-13662777-C-T
• rs781199391
• NM_001297563.2:c.269C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001297563.2(TCEANC):​c.269C>T​(p.Pro90Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,209,715 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.000013 (0 hom. 5 hem.)
• Consequence: TCEANC NM_001297563.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.556
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.075778455).
• BS2: High Hemizygotes in GnomAdExome4 at 5 XL gene

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.269C>T	p.Pro90Leu	missense	Exon 5 of 5	NP_001284492.1	Q8N8B7-1
	TCEANC	NM_152634.4		c.359C>T	p.Pro120Leu	missense	Exon 4 of 4	NP_689847.2
	TCEANC	NM_001297564.2		c.269C>T	p.Pro90Leu	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.269C>T	p.Pro90Leu	missense	Exon 5 of 5	ENSP00000512421.1	Q8N8B7-1
	TCEANC	ENST00000544987.3	TSL:5	c.359C>T	p.Pro120Leu	missense	Exon 4 of 4	ENSP00000440038.2	Q8N8B7-2
	TCEANC	ENST00000380600.2	TSL:3	c.269C>T	p.Pro90Leu	missense	Exon 3 of 3	ENSP00000369974.1	Q8N8B7-1

Frequencies

GnomAD3 genomes AF: 0.00000892 AC: 1 AN: 112144 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000167 AC: 3 AN: 179131 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000369

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000250

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000128 AC: 14 AN: 1097571 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 5 AN XY: 363027

African (AFR) AF: 0.00 AC: 0 AN: 26395

American (AMR) AF: 0.0000285 AC: 1 AN: 35135

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19375

East Asian (EAS) AF: 0.00 AC: 0 AN: 30197

South Asian (SAS) AF: 0.00 AC: 0 AN: 54043

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40498

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

European-Non Finnish (NFE) AF: 0.0000143 AC: 12 AN: 841721

Other (OTH) AF: 0.0000217 AC: 1 AN: 46071

GnomAD4 genome AF: 0.00000892 AC: 1 AN: 112144 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34314

African (AFR) AF: 0.00 AC: 0 AN: 30828

American (AMR) AF: 0.00 AC: 0 AN: 10564

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2658

East Asian (EAS) AF: 0.00 AC: 0 AN: 3602

South Asian (SAS) AF: 0.00 AC: 0 AN: 2738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6088

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53233

Other (OTH) AF: 0.00 AC: 0 AN: 1505

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000828 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	5.9
DANN	Benign	0.72
DEOGEN2	Benign	0.018	T
FATHMM_MKL	Benign	0.080	N
LIST_S2	Benign	0.59	T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.56
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.090
Sift	Benign	0.16	T
Sift4G	Benign	0.16	T
Polyphen		0.0050	B
Vest4		0.10
MVP		0.65
ClinPred		0.050	T
GERP RS		4.3
Varity_R		0.091
gMVP		0.12
Mutation Taster		=92/8	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: rs781199391; hg19: chrX-13680896;