X-13662987-G-A

Variant names:

• chrX-13662987-G-A
• rs776867676
• NM_001297563.2:c.479G>A

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.479G>A​(p.Gly160Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,097,562 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000011 (0 hom. 2 hem.)
• Consequence: TCEANC NM_001297563.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.232

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=0.034087032).
• BP6: Variant X-13662987-G-A is Benign according to our data. Variant chrX-13662987-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3454046.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEANC	NM_001297563.2	c.479G>A	p.Gly160Asp	missense_variant	Exon 5 of 5	ENST00000696128.1	NP_001284492.1
TCEANC	NM_152634.4	c.569G>A	p.Gly190Asp	missense_variant	Exon 4 of 4		NP_689847.2
TCEANC	NM_001297564.2	c.479G>A	p.Gly160Asp	missense_variant	Exon 3 of 3		NP_001284493.1
TCEANC	XM_017029316.2	c.569G>A	p.Gly190Asp	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.479G>A	p.Gly160Asp	missense_variant	Exon 5 of 5		NM_001297563.2	ENSP00000512421.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD3 exomes AF: 0.0000607 AC: 11 AN: 181189 Hom.: 0 AF XY: 0.0000298 AC XY: 2 AN XY: 67221

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000402

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000109 AC: 12 AN: 1097562 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 2 AN XY: 363020

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000341

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

Bravo AF: 0.0000189

ExAC AF: 0.0000496 AC: 6

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jun 28, 2024

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	0.070
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.68
DANN	Benign	0.12
DEOGEN2	Benign	0.0013	T;.
FATHMM_MKL	Benign	0.024	N
LIST_S2	Benign	0.50	T;T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.034	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.26	N;.
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.31	N;.
REVEL	Benign	0.055
Sift	Benign	0.53	T;.
Sift4G	Benign	0.80	T;T
Polyphen		0.0	B;B
Vest4		0.040
MutPred		0.34		Loss of catalytic residue at P156 (P = 0.0914);.;
MVP		0.36
ClinPred		0.25	T
GERP RS		1.8
Varity_R		0.074
gMVP		0.18

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: rs776867676; hg19: chrX-13681106;