chrX-13663220-C-G

Variant names:

• chrX-13663220-C-G
• rs376413776
• NM_001297563.2:c.712C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001297563.2(TCEANC):​c.712C>G​(p.His238Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000916 in 1,091,843 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a pathogenic 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. H238Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: TCEANC NM_001297563.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.58
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.796

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.712C>G	p.His238Asp	missense	Exon 5 of 5	NP_001284492.1	Q8N8B7-1
	TCEANC	NM_152634.4		c.802C>G	p.His268Asp	missense	Exon 4 of 4	NP_689847.2
	TCEANC	NM_001297564.2		c.712C>G	p.His238Asp	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.712C>G	p.His238Asp	missense	Exon 5 of 5	ENSP00000512421.1	Q8N8B7-1
	TCEANC	ENST00000544987.3	TSL:5	c.802C>G	p.His268Asp	missense	Exon 4 of 4	ENSP00000440038.2	Q8N8B7-2
	TCEANC	ENST00000380600.2	TSL:3	c.712C>G	p.His238Asp	missense	Exon 3 of 3	ENSP00000369974.1	Q8N8B7-1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.16e-7 AC: 1 AN: 1091843 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 358033

African (AFR) AF: 0.0000380 AC: 1 AN: 26290

American (AMR) AF: 0.00 AC: 0 AN: 34359

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19263

East Asian (EAS) AF: 0.00 AC: 0 AN: 30052

South Asian (SAS) AF: 0.00 AC: 0 AN: 52986

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40186

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4129

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 838675

Other (OTH) AF: 0.00 AC: 0 AN: 45903

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.033	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T
M_CAP	Pathogenic	0.59	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.6
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.19
Sift	Benign	0.031	D
Sift4G	Benign	0.064	T
Polyphen		1.0	D
Vest4		0.49
MutPred		0.28		Loss of MoRF binding (P = 0.0564)
MVP		0.60
ClinPred		0.95	D
GERP RS		5.6
Varity_R		0.83
gMVP		0.48
Mutation Taster		=61/39	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: rs376413776; hg19: chrX-13681339;