Genetic Variant NM_004780.3:c.346G>A (chrX-103630262-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004780.3(TCEAL1):c.346G>A(p.Asp116Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000033 in 1,210,401 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

TCEAL1
NM_004780.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.39

Variant links:

Genes affected

TCEAL1 (HGNC:11616): (transcription elongation factor A like 1) This gene encodes a member of the transcription elongation factor A (SII)-like (TCEAL) gene family. Members of this family may function as nuclear phosphoproteins that modulate transcription in a promoter context-dependent manner. The encoded protein is similar to transcription elongation factor A/transcription factor SII and contains a zinc finger-like motif as well as a sequence related to the transcription factor SII Pol II-binding region. It may exert its effects via protein-protein interactions with other transcriptional regulators rather than via direct binding of DNA. Multiple family members are located on the X chromosome. Alternative splicing results in multiple transcript variants encoding a single isoform. [provided by RefSeq, Jul 2008]

TCEAL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL1	NM_004780.3 link	c.346G>A	p.Asp116Asn	missense_variant	Exon 3 of 3	ENST00000372625.8	NP_004771.2	Q15170
TCEAL1	NM_001006639.2 link	c.346G>A	p.Asp116Asn	missense_variant	Exon 3 of 3		NP_001006640.1	Q15170
TCEAL1	NM_001006640.2 link	c.346G>A	p.Asp116Asn	missense_variant	Exon 3 of 3		NP_001006641.1	Q15170

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TCEAL1	ENST00000372625.8 link	c.346G>A	p.Asp116Asn	missense_variant	Exon 3 of 3	1	NM_004780.3	ENSP00000361708.3	Q15170
TCEAL1	ENST00000372624.3 link	c.346G>A	p.Asp116Asn	missense_variant	Exon 3 of 3	1		ENSP00000361707.3	Q15170
TCEAL1	ENST00000372626.7 link	c.346G>A	p.Asp116Asn	missense_variant	Exon 3 of 3	2		ENSP00000361709.3	Q15170
TCEAL1	ENST00000469820.1 link	n.*45G>A		downstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112150

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34318

show subpopulations

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000545

AC:

AN:

183451

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67889

show subpopulations

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 SAS 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:

0.00000182

AC:

AN:

1098251

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363605

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000237

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112150

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34318

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

See cases

Uncertain:1

Aug 02, 2022

Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Uncertain

DANN

Uncertain

1.0

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.79

.;.;T

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.71

D;D;D

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Benign

0.14

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.053

T;T;T

Polyphen

0.59

P;P;P

Vest4

0.33

MutPred

0.86

Gain of MoRF binding (P = 0.0474);Gain of MoRF binding (P = 0.0474);Gain of MoRF binding (P = 0.0474);

MVP

0.77

MPC

0.88

ClinPred

0.69

GERP RS

3.9

gMVP

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over