chrX-102126839-A-T

Variant names:

• chrX-102126839-A-T
• rs1293879969
• NM_080390.4:c.9A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_080390.4(TCEAL2):​c.9A>T​(p.Lys3Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000535 in 112,098 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000054 (0 hom., 1 hem., cov: 24)
• Consequence: TCEAL2 NM_080390.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.403
• Publications: 0 publications found

Genes affected

TCEAL2 (HGNC:29818): (transcription elongation factor A like 2) This gene encodes a member of the transcription elongation factor A (SII)-like (TCEAL) gene family. Members of this family contain TFA domains and may function as nuclear phosphoproteins that modulate transcription in a promoter context-dependent manner. Multiple family members are located on the X chromosome. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.062070876).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080390.4. 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
	TCEAL2	NM_080390.4	MANE Select	c.9A>T	p.Lys3Asn	missense	Exon 3 of 3	NP_525129.1	Q9H3H9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL2	ENST00000372780.6	TSL:1 MANE Select	c.9A>T	p.Lys3Asn	missense	Exon 3 of 3	ENSP00000361866.1	Q9H3H9
	TCEAL2	ENST00000476749.1	TSL:1	n.794A>T		non_coding_transcript_exon	Exon 2 of 2
	TCEAL2	ENST00000329035.2	TSL:5	c.9A>T	p.Lys3Asn	missense	Exon 3 of 3	ENSP00000332359.2	Q9H3H9

Frequencies

GnomAD3 genomes AF: 0.0000535 AC: 6 AN: 112098 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

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: 0.000113

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000535 AC: 6 AN: 112098 Hom.: 0 Cov.: 24 AF XY: 0.0000292 AC XY: 1 AN XY: 34302

African (AFR) AF: 0.00 AC: 0 AN: 30825

American (AMR) AF: 0.00 AC: 0 AN: 10621

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2642

East Asian (EAS) AF: 0.00 AC: 0 AN: 3572

South Asian (SAS) AF: 0.00 AC: 0 AN: 2694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 236

European-Non Finnish (NFE) AF: 0.000113 AC: 6 AN: 53133

Other (OTH) AF: 0.00 AC: 0 AN: 1510

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

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	0.13
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.9
DANN	Benign	0.95
DEOGEN2	Benign	0.027	T
FATHMM_MKL	Benign	0.049	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.00096	T
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.40
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.036
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.024	D
Polyphen		0.0010	B
Vest4		0.087
MutPred		0.46		Loss of methylation at K3 (P = 0.0017)
MVP		0.068
MPC		0.25
ClinPred		0.041	T
GERP RS		0.76
Varity_R		0.20
gMVP		0.082
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1293879969; hg19: chrX-101381811;