X-13662765-C-T

Variant names:

• chrX-13662765-C-T
• rs1569218021
• NM_001297563.2:c.257C>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.257C>T​(p.Ala86Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,097,516 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000018 (0 hom. 7 hem.)
• Consequence: TCEANC NM_001297563.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.67
• 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=0.094789386).
• BS2: High Hemizygotes in GnomAdExome4 at 7 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.257C>T	p.Ala86Val	missense	Exon 5 of 5	NP_001284492.1	Q8N8B7-1
	TCEANC	NM_152634.4		c.347C>T	p.Ala116Val	missense	Exon 4 of 4	NP_689847.2
	TCEANC	NM_001297564.2		c.257C>T	p.Ala86Val	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.257C>T	p.Ala86Val	missense	Exon 5 of 5	ENSP00000512421.1	Q8N8B7-1
	TCEANC	ENST00000544987.3	TSL:5	c.347C>T	p.Ala116Val	missense	Exon 4 of 4	ENSP00000440038.2	Q8N8B7-2
	TCEANC	ENST00000380600.2	TSL:3	c.257C>T	p.Ala86Val	missense	Exon 3 of 3	ENSP00000369974.1	Q8N8B7-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.0000182 AC: 20 AN: 1097516 Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 7 AN XY: 362970

African (AFR) AF: 0.00 AC: 0 AN: 26397

American (AMR) AF: 0.00 AC: 0 AN: 35133

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19374

East Asian (EAS) AF: 0.00 AC: 0 AN: 30198

South Asian (SAS) AF: 0.00 AC: 0 AN: 54053

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40495

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.0000238 AC: 20 AN: 841652

Other (OTH) AF: 0.00 AC: 0 AN: 46077

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

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	0.078
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.3
DANN	Benign	0.83
DEOGEN2	Benign	0.012	T
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.7
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.97	N
REVEL	Benign	0.077
Sift	Benign	0.078	T
Sift4G	Benign	0.11	T
Polyphen		0.063	B
Vest4		0.048
MutPred		0.51		Gain of catalytic residue at A86 (P = 0.0295)
MVP		0.37
ClinPred		0.074	T
GERP RS		3.5
Varity_R		0.052
gMVP		0.18
Mutation Taster		=94/6	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: rs1569218021; hg19: chrX-13680884; COSMIC: COSV59039754; COSMIC: COSV59039754;