rs1263281146

Variant names:

• chrX-103357814-A-T
• rs1263281146
• NM_016303.3:c.130A>T

Variant summary

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

The NM_016303.3(TCEAL9):​c.130A>T​(p.Thr44Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000909 in 1,209,822 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0000073 (0 hom. 5 hem.)
• Consequence: TCEAL9 NM_016303.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22
• Publications: 0 publications found

Genes affected

TCEAL9 (HGNC:30084): (transcription elongation factor A like 9) The globular WW domain is composed of 38 to 40 semiconserved amino acids shared by proteins of diverse functions including structural, regulatory, and signaling proteins. The domain is involved in mediating protein-protein interactions through the binding of polyproline ligands. This gene encodes a WW domain binding protein. This gene also encodes a domain with similarity to the transcription elongation factor A, SII-related family. Alternative splicing results in multiple transcript variants encoding a single isoform. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.038300335).
• BS2: High Hemizygotes in GnomAdExome4 at 5 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016303.3. 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
	TCEAL9	NM_016303.3	MANE Select	c.130A>T	p.Thr44Ser	missense	Exon 3 of 3	NP_057387.1	Q9UHQ7
	TCEAL9	NM_001006612.2		c.130A>T	p.Thr44Ser	missense	Exon 3 of 3	NP_001006613.1	Q9UHQ7
	TCEAL9	NM_001006613.2		c.130A>T	p.Thr44Ser	missense	Exon 2 of 2	NP_001006614.1	Q9UHQ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL9	ENST00000372661.6	TSL:1 MANE Select	c.130A>T	p.Thr44Ser	missense	Exon 3 of 3	ENSP00000361745.3	Q9UHQ7
	TCEAL9	ENST00000372656.5	TSL:2	c.130A>T	p.Thr44Ser	missense	Exon 2 of 2	ENSP00000361740.3	Q9UHQ7
	TCEAL9	ENST00000646896.1		c.130A>T	p.Thr44Ser	missense	Exon 1 of 1	ENSP00000496422.1	Q9UHQ7

Frequencies

GnomAD3 genomes AF: 0.0000269 AC: 3 AN: 111589 Hom.: 0 Cov.: 23

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: 0.0000565

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000545 AC: 1 AN: 183334 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: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000728 AC: 8 AN: 1098233 Hom.: 0 Cov.: 31 AF XY: 0.0000138 AC XY: 5 AN XY: 363595

African (AFR) AF: 0.00 AC: 0 AN: 26403

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30201

South Asian (SAS) AF: 0.00 AC: 0 AN: 54146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000950 AC: 8 AN: 842136

Other (OTH) AF: 0.00 AC: 0 AN: 46096

GnomAD4 genome AF: 0.0000269 AC: 3 AN: 111589 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33749

African (AFR) AF: 0.00 AC: 0 AN: 30665

American (AMR) AF: 0.00 AC: 0 AN: 10490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2650

East Asian (EAS) AF: 0.00 AC: 0 AN: 3556

South Asian (SAS) AF: 0.00 AC: 0 AN: 2631

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6048

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

European-Non Finnish (NFE) AF: 0.0000565 AC: 3 AN: 53122

Other (OTH) AF: 0.00 AC: 0 AN: 1507

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

EpiCase AF: 0.000109

EpiControl AF: 0.00

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	0.088
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.98
CADD	Benign	12
DANN	Benign	0.24
DEOGEN2	Benign	0.0054	T
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.16	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.93	T
PhyloP100		1.2
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.024
Sift	Benign	0.87	T
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.22		Loss of methylation at K42 (P = 0.0848)
MVP		0.18
MPC		0.049
ClinPred		0.032	T
GERP RS		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.041
gMVP		0.11
Mutation Taster		=96/4	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: rs1263281146; hg19: chrX-102612742;