NM_001297563.2:c.314C>T

Variant names:

• chrX-13662822-C-T
• rs199942414
• NM_001297563.2:c.314C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001297563.2(TCEANC):​c.314C>T​(p.Pro105Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00058 in 1,209,817 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 207 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., 10 hem., cov: 23)
  • Exomes 𝑓: 0.00061 (0 hom. 197 hem.)
• Consequence: TCEANC NM_001297563.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.344
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019588262).
• BP6: Variant X-13662822-C-T is Benign according to our data. Variant chrX-13662822-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2587946.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 10 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.314C>T	p.Pro105Leu	missense	Exon 5 of 5	NP_001284492.1	Q8N8B7-1
	TCEANC	NM_152634.4		c.404C>T	p.Pro135Leu	missense	Exon 4 of 4	NP_689847.2
	TCEANC	NM_001297564.2		c.314C>T	p.Pro105Leu	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.314C>T	p.Pro105Leu	missense	Exon 5 of 5	ENSP00000512421.1	Q8N8B7-1
	TCEANC	ENST00000544987.3	TSL:5	c.404C>T	p.Pro135Leu	missense	Exon 4 of 4	ENSP00000440038.2	Q8N8B7-2
	TCEANC	ENST00000380600.2	TSL:3	c.314C>T	p.Pro105Leu	missense	Exon 3 of 3	ENSP00000369974.1	Q8N8B7-1

Frequencies

GnomAD3 genomes AF: 0.000258 AC: 29 AN: 112286 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000648

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: 0.000507

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000268 AC: 48 AN: 179342 AF XY: 0.000198

Gnomad AFR exome AF: 0.0000816

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000631

Gnomad NFE exome AF: 0.000550

Gnomad OTH exome AF: 0.000453

GnomAD4 exome AF: 0.000613 AC: 673 AN: 1097531 Hom.: 0 Cov.: 31 AF XY: 0.000543 AC XY: 197 AN XY: 362973

African (AFR) AF: 0.000114 AC: 3 AN: 26396

American (AMR) AF: 0.00 AC: 0 AN: 35131

Ashkenazi Jewish (ASJ) AF: 0.0000516 AC: 1 AN: 19369

East Asian (EAS) AF: 0.00 AC: 0 AN: 30196

South Asian (SAS) AF: 0.00 AC: 0 AN: 54042

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40501

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4133

European-Non Finnish (NFE) AF: 0.000767 AC: 646 AN: 841699

Other (OTH) AF: 0.000478 AC: 22 AN: 46064

GnomAD4 genome AF: 0.000258 AC: 29 AN: 112286 Hom.: 0 Cov.: 23 AF XY: 0.000290 AC XY: 10 AN XY: 34442

African (AFR) AF: 0.0000648 AC: 2 AN: 30843

American (AMR) AF: 0.00 AC: 0 AN: 10585

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2657

East Asian (EAS) AF: 0.00 AC: 0 AN: 3603

South Asian (SAS) AF: 0.00 AC: 0 AN: 2761

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6107

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

European-Non Finnish (NFE) AF: 0.000507 AC: 27 AN: 53296

Other (OTH) AF: 0.00 AC: 0 AN: 1507

Alfa AF: 0.000610 Hom.: 23

Bravo AF: 0.000272

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000346 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000778 AC: 5

ExAC AF: 0.000248 AC: 30

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.051
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.67
DEOGEN2	Benign	0.0087	T
FATHMM_MKL	Benign	0.0018	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.020	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	N
PhyloP100		0.34
PrimateAI	Benign	0.17	T
PROVEAN	Benign	0.87	N
REVEL	Benign	0.023
Sift	Benign	0.40	T
Sift4G	Benign	0.58	T
Polyphen		0.0	B
Vest4		0.024
MVP		0.56
ClinPred		0.0089	T
GERP RS		-2.4
Varity_R		0.031
gMVP		0.086
Mutation Taster		=100/0	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: rs199942414; hg19: chrX-13680941;