chrX-103274116-C-T

Variant names:

• chrX-103274116-C-T
• rs995975091
• NM_001012979.3:c.448G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001012979.3(TCEAL5):​c.448G>A​(p.Gly150Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000198 in 1,210,283 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., 4 hem., cov: 23)
  • Exomes 𝑓: 0.000010 (0 hom. 2 hem.)
• Consequence: TCEAL5 NM_001012979.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.731
• Publications: 0 publications found

Genes affected

TCEAL5 (HGNC:22282): (transcription elongation factor A like 5) This gene, which is located on the X chromosome, encodes a protein which contains a BEX (brain expressed X-liked like family) domain. This domain is found in proteins encoded by the TCEAL elongation factor (transcription elongation factor A (SII)-like) gene family also located on the X chromosome. The coding region for this gene is located entirely in the terminal exon. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12729812).
• BS2: High Hemizygotes in GnomAd4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012979.3. 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
	TCEAL5	NM_001012979.3	MANE Select	c.448G>A	p.Gly150Arg	missense	Exon 3 of 3	NP_001012997.1	Q5H9L2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL5	ENST00000372680.2	TSL:1 MANE Select	c.448G>A	p.Gly150Arg	missense	Exon 3 of 3	ENSP00000361765.1	Q5H9L2
	TCEAL5	ENST00000909247.1		c.448G>A	p.Gly150Arg	missense	Exon 3 of 3	ENSP00000579306.1
	TCEAL5	ENST00000909248.1		c.448G>A	p.Gly150Arg	missense	Exon 2 of 2	ENSP00000579307.1

Frequencies

GnomAD3 genomes AF: 0.000116 AC: 13 AN: 112027 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.0000325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00103

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: 0.00

Gnomad OTH AF: 0.000660

GnomAD2 exomes AF: 0.00000545 AC: 1 AN: 183527 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000221

GnomAD4 exome AF: 0.0000100 AC: 11 AN: 1098256 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 2 AN XY: 363614

African (AFR) AF: 0.00 AC: 0 AN: 26400

American (AMR) AF: 0.000114 AC: 4 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.00 AC: 0 AN: 54148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4131

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842150

Other (OTH) AF: 0.000152 AC: 7 AN: 46094

GnomAD4 genome AF: 0.000116 AC: 13 AN: 112027 Hom.: 0 Cov.: 23 AF XY: 0.000117 AC XY: 4 AN XY: 34185

African (AFR) AF: 0.0000325 AC: 1 AN: 30760

American (AMR) AF: 0.00103 AC: 11 AN: 10646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2658

East Asian (EAS) AF: 0.00 AC: 0 AN: 3582

South Asian (SAS) AF: 0.00 AC: 0 AN: 2659

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53174

Other (OTH) AF: 0.000660 AC: 1 AN: 1516

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000355

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	0.19
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0038	T
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.78	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.73
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.057
Sift	Benign	0.070	T
Sift4G	Benign	0.21	T
Polyphen		0.97	D
Vest4		0.26
MutPred		0.50		Gain of MoRF binding (P = 0.0202)
MVP		0.11
MPC		1.6
ClinPred		0.43	T
GERP RS		1.9
Varity_R		0.11
gMVP		0.026
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: rs995975091; hg19: chrX-102529044;