Genetic Variant TCEAL3:p.Gln191His (chrX-103609637-G-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032926.3(TCEAL3):c.573G>C(p.Gln191His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000326 in 919,993 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 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: not found (cov: 23)

Exomes 𝑓: 0.000033 ( 0 hom. 4 hem. )

Consequence

TCEAL3
NM_032926.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0500

Publications

2 publications found

Variant links:

Genes affected

TCEAL3 (HGNC:28247): (transcription elongation factor A like 3) 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. Alternative splicing results in multiple transcript variants encoding a single isoform. [provided by RefSeq, Jul 2008]

TCEAL3 links:

ENSG00000304280 (HGNC:):

ENSG00000304280 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.1271345).

BS2

High Hemizygotes in GnomAdExome4 at 4 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032926.3. 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
	TCEAL3	NM_032926.3	MANE Select	c.573G>C	p.Gln191His	missense	Exon 3 of 3	NP_116315.1	Q969E4
	TCEAL3	NM_001006933.2		c.573G>C	p.Gln191His	missense	Exon 3 of 3	NP_001006934.1	Q969E4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCEAL3	ENST00000372627.10	TSL:1 MANE Select	c.573G>C	p.Gln191His	missense	Exon 3 of 3	ENSP00000361710.5	Q969E4
TCEAL3	ENST00000243286.7	TSL:1	c.573G>C	p.Gln191His	missense	Exon 3 of 3	ENSP00000243286.3	Q969E4
TCEAL3	ENST00000372628.5	TSL:5	c.573G>C	p.Gln191His	missense	Exon 3 of 3	ENSP00000361711.1	Q969E4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000110

AC:

AN:

91305

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000251

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000326

AC:

AN:

919993

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

293395

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22951

American (AMR)

AF:

0.00

AC:

AN:

32416

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17148

East Asian (EAS)

AF:

0.00

AC:

AN:

28744

South Asian (SAS)

AF:

0.00

AC:

AN:

47820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38216

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3510

European-Non Finnish (NFE)

AF:

0.0000435

AC:

AN:

689107

Other (OTH)

AF:

0.00

AC:

AN:

40081

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.039

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.70

M_CAP

Benign

0.0072

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

-0.050

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.1

REVEL

Benign

0.16

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.052

Polyphen

0.013

Vest4

0.35

MutPred

0.22

Gain of catalytic residue at Q191 (P = 0.0565)

MVP

0.35

MPC

0.82

ClinPred

0.16

GERP RS

-2.0

Varity_R

0.15

gMVP

0.036

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over