X-102126903-C-T

Variant names:

• chrX-102126903-C-T
• rs149647049
• NM_080390.4:c.73C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_080390.4(TCEAL2):​c.73C>T​(p.Pro25Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000934 in 1,210,321 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 384 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00077 (0 hom., 16 hem., cov: 23)
  • Exomes 𝑓: 0.00095 (0 hom. 368 hem.)
• Consequence: TCEAL2 NM_080390.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.954
• Publications: 3 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005600959).
• BS2: High Hemizygotes in GnomAd4 at 16 gene

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.73C>T	p.Pro25Ser	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.73C>T	p.Pro25Ser	missense	Exon 3 of 3	ENSP00000361866.1	Q9H3H9
	TCEAL2	ENST00000329035.2	TSL:5	c.73C>T	p.Pro25Ser	missense	Exon 3 of 3	ENSP00000332359.2	Q9H3H9
	TCEAL2	ENST00000902218.1		c.73C>T	p.Pro25Ser	missense	Exon 3 of 3	ENSP00000572277.1

Frequencies

GnomAD3 genomes AF: 0.000766 AC: 86 AN: 112318 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000942

Gnomad ASJ AF: 0.00113

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000365

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00143

Gnomad OTH AF: 0.000660

GnomAD2 exomes AF: 0.00100 AC: 184 AN: 183215 AF XY: 0.000931

Gnomad AFR exome AF: 0.0000760

Gnomad AMR exome AF: 0.00106

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00156

Gnomad OTH exome AF: 0.00331

GnomAD4 exome AF: 0.000952 AC: 1045 AN: 1097948 Hom.: 0 Cov.: 31 AF XY: 0.00101 AC XY: 368 AN XY: 363332

African (AFR) AF: 0.000114 AC: 3 AN: 26393

American (AMR) AF: 0.00114 AC: 40 AN: 35176

Ashkenazi Jewish (ASJ) AF: 0.000258 AC: 5 AN: 19380

East Asian (EAS) AF: 0.00 AC: 0 AN: 30203

South Asian (SAS) AF: 0.000499 AC: 27 AN: 54077

European-Finnish (FIN) AF: 0.0000493 AC: 2 AN: 40533

Middle Eastern (MID) AF: 0.00266 AC: 11 AN: 4136

European-Non Finnish (NFE) AF: 0.00110 AC: 927 AN: 841971

Other (OTH) AF: 0.000651 AC: 30 AN: 46079

GnomAD4 genome AF: 0.000765 AC: 86 AN: 112373 Hom.: 0 Cov.: 23 AF XY: 0.000463 AC XY: 16 AN XY: 34589

African (AFR) AF: 0.000129 AC: 4 AN: 30932

American (AMR) AF: 0.0000941 AC: 1 AN: 10628

Ashkenazi Jewish (ASJ) AF: 0.00113 AC: 3 AN: 2651

East Asian (EAS) AF: 0.00 AC: 0 AN: 3557

South Asian (SAS) AF: 0.000366 AC: 1 AN: 2731

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6167

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00143 AC: 76 AN: 53270

Other (OTH) AF: 0.000651 AC: 1 AN: 1535

Alfa AF: 0.00113 Hom.: 29

Bravo AF: 0.000793

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000346 AC: 1

ESP6500AA AF: 0.000522 AC: 2

ESP6500EA AF: 0.00119 AC: 8

ExAC AF: 0.00107 AC: 130

EpiCase AF: 0.00240

EpiControl AF: 0.00202

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	0.072
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.97
CADD	Benign	10
DANN	Benign	0.85
DEOGEN2	Benign	0.0030	T
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.0056	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.95
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.030	N
REVEL	Benign	0.0030
Sift	Benign	0.096	T
Sift4G	Benign	0.28	T
Polyphen		0.0070	B
Vest4		0.057
MVP		0.068
MPC		0.32
ClinPred		0.0087	T
GERP RS		0.55
Varity_R		0.034
gMVP		0.012
Mutation Taster		=100/0	polymorphism (auto)

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: rs149647049; hg19: chrX-101381875; COSMIC: COSV100216195; COSMIC: COSV100216195;