X-13662822-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 2587946.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-13662822-C-T is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEANC	NM_001297563.2	c.314C>T	p.Pro105Leu	missense_variant	Exon 5 of 5	ENST00000696128.1	NP_001284492.1
TCEANC	NM_152634.4	c.404C>T	p.Pro135Leu	missense_variant	Exon 4 of 4		NP_689847.2
TCEANC	NM_001297564.2	c.314C>T	p.Pro105Leu	missense_variant	Exon 3 of 3		NP_001284493.1
TCEANC	XM_017029316.2	c.404C>T	p.Pro135Leu	missense_variant	Exon 4 of 4		XP_016884805.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEANC	ENST00000696128.1	c.314C>T	p.Pro105Leu	missense_variant	Exon 5 of 5		NM_001297563.2	ENSP00000512421.1

Frequencies

GnomAD3 genomes AF: 0.000258 AC: 29 AN: 112286 Hom.: 0 Cov.: 23 AF XY: 0.000290 AC XY: 10 AN XY: 34442

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

GnomAD3 exomes AF: 0.000268 AC: 48 AN: 179342 Hom.: 0 AF XY: 0.000198 AC XY: 13 AN XY: 65520

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 SAS 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

Gnomad4 AFR exome AF: 0.000114

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000516

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000247

Gnomad4 NFE exome AF: 0.000767

Gnomad4 OTH exome AF: 0.000478

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

Gnomad4 AFR AF: 0.0000648

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000507

Gnomad4 OTH AF: 0.00

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jun 22, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.020	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.7	N;.
PrimateAI	Benign	0.17	T
PROVEAN	Benign	0.87	N;.
REVEL	Benign	0.023
Sift	Benign	0.40	T;.
Sift4G	Benign	0.58	T;T
Polyphen		0.0	B;B
Vest4		0.024
MVP		0.56
ClinPred		0.0089	T
GERP RS		-2.4
Varity_R		0.031
gMVP		0.086

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

Publications

LitVar

Other links and lift over

dbSNP: rs199942414; hg19: chrX-13680941;