chrX-13663329-C-T

Variant names:

• chrX-13663329-C-T
• rs755901692
• NM_001297563.2:c.821C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001297563.2(TCEANC):​c.821C>T​(p.Thr274Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000502 in 1,194,561 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 14 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000053 (0 hom. 13 hem.)
• Consequence: TCEANC NM_001297563.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.63
• Publications: 4 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 -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 13 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.821C>T	p.Thr274Met	missense	Exon 5 of 5	NP_001284492.1	Q8N8B7-1
	TCEANC	NM_152634.4		c.911C>T	p.Thr304Met	missense	Exon 4 of 4	NP_689847.2
	TCEANC	NM_001297564.2		c.821C>T	p.Thr274Met	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.821C>T	p.Thr274Met	missense	Exon 5 of 5	ENSP00000512421.1	Q8N8B7-1
	TCEANC	ENST00000544987.3	TSL:5	c.911C>T	p.Thr304Met	missense	Exon 4 of 4	ENSP00000440038.2	Q8N8B7-2
	TCEANC	ENST00000380600.2	TSL:3	c.821C>T	p.Thr274Met	missense	Exon 3 of 3	ENSP00000369974.1	Q8N8B7-1

Frequencies

GnomAD3 genomes AF: 0.0000268 AC: 3 AN: 111995 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000950

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: 0.0000376

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000656 AC: 1 AN: 152360 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000864

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000527 AC: 57 AN: 1082566 Hom.: 0 Cov.: 35 AF XY: 0.0000369 AC XY: 13 AN XY: 351920

African (AFR) AF: 0.0000383 AC: 1 AN: 26110

American (AMR) AF: 0.00 AC: 0 AN: 32912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19050

East Asian (EAS) AF: 0.00 AC: 0 AN: 29683

South Asian (SAS) AF: 0.00 AC: 0 AN: 51695

European-Finnish (FIN) AF: 0.0000252 AC: 1 AN: 39688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4114

European-Non Finnish (NFE) AF: 0.0000636 AC: 53 AN: 833724

Other (OTH) AF: 0.0000439 AC: 2 AN: 45590

GnomAD4 genome AF: 0.0000268 AC: 3 AN: 111995 Hom.: 0 Cov.: 23 AF XY: 0.0000293 AC XY: 1 AN XY: 34159

African (AFR) AF: 0.00 AC: 0 AN: 30788

American (AMR) AF: 0.0000950 AC: 1 AN: 10523

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2649

East Asian (EAS) AF: 0.00 AC: 0 AN: 3605

South Asian (SAS) AF: 0.00 AC: 0 AN: 2711

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6039

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.0000376 AC: 2 AN: 53248

Other (OTH) AF: 0.00 AC: 0 AN: 1503

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.00000834 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	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.64	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		3.6
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.21
Sift	Benign	0.031	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.96	D
Vest4		0.33
MutPred		0.62		Gain of phosphorylation at Y273 (P = 0.105)
MVP		0.40
ClinPred		0.99	D
GERP RS		3.6
Varity_R		0.35
gMVP		0.23
Mutation Taster		=95/5	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: rs755901692; hg19: chrX-13681448; COSMIC: COSV59039293; COSMIC: COSV59039293;