Genetic Variant TCEAL6:p.Lys71Arg (chrX-102141120-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001006938.3(TCEAL6):c.212A>G(p.Lys71Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,210,799 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 0.000036 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000082 ( 0 hom. 3 hem. )

Consequence

TCEAL6
NM_001006938.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0570

Publications

0 publications found

Variant links:

Genes affected

TCEAL6 (HGNC:24553): (transcription elongation factor A like 6) Predicted to enable WW domain binding activity. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TCEAL6 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.039409906).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001006938.3. 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
	TCEAL6	NM_001006938.3		c.212A>G	p.Lys71Arg	missense	Exon 3 of 3	NP_001006939.2	Q6IPX3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCEAL6	ENST00000372774.8	TSL:1	c.212A>G	p.Lys71Arg	missense	Exon 3 of 4	ENSP00000361860.4	Q6IPX3
	TCEAL6	ENST00000372773.2	TSL:3	c.212A>G	p.Lys71Arg	missense	Exon 3 of 4	ENSP00000361859.2	Q6IPX3

Frequencies

GnomAD3 genomes

AF:

0.0000356

AC:

AN:

112495

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000967

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000284

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000164

AC:

AN:

183482

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000144

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000819

AC:

AN:

1098250

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

363608

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26398

American (AMR)

AF:

0.00

AC:

AN:

35206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19385

East Asian (EAS)

AF:

0.000132

AC:

AN:

30206

South Asian (SAS)

AF:

0.00

AC:

AN:

54144

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40533

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000356

AC:

AN:

842143

Other (OTH)

AF:

0.0000217

AC:

AN:

46098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.417

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

AF:

0.0000355

AC:

AN:

112549

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34699

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

31098

American (AMR)

AF:

0.00

AC:

AN:

10729

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2655

East Asian (EAS)

AF:

0.000285

AC:

AN:

3506

South Asian (SAS)

AF:

0.00

AC:

AN:

2673

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6229

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53212

Other (OTH)

AF:

0.00

AC:

AN:

1546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000165

AC:

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

Benign

0.096

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.98

CADD

Benign

8.2

(source)

DANN

Benign

0.96

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.077

M_CAP

Benign

0.0024

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.1

PhyloP100

0.057

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.6

REVEL

Benign

0.034

Sift

Benign

0.13

Sift4G

Benign

0.29

Polyphen

0.0050

Vest4

0.073

MutPred

0.43

Loss of ubiquitination at K71 (P = 0.0118)

MVP

0.16

MPC

0.15

ClinPred

0.058

GERP RS

1.3

gMVP

0.0061

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over