Genetic Variant TCEAL6:p.Pro4Pro (chrX-102141320-G-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001006938.3(TCEAL6):c.12C>G(p.Pro4Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 1,205,144 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 202 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., 16 hem., cov: 24)

Exomes 𝑓: 0.00049 ( 0 hom. 186 hem. )

Consequence

TCEAL6
NM_001006938.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.70

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 made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant X-102141320-G-C is Benign according to our data. Variant chrX-102141320-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2661077.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.7 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCEAL6	NM_001006938.3 link	c.12C>G	p.Pro4Pro	synonymous_variant	Exon 3 of 3		NP_001006939.2	A0A024RCH0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCEAL6	ENST00000372774.8 link	c.12C>G	p.Pro4Pro	synonymous_variant	Exon 3 of 4	1		ENSP00000361860.4		Q6IPX3
TCEAL6	ENST00000372773.2 link	c.12C>G	p.Pro4Pro	synonymous_variant	Exon 3 of 4	3		ENSP00000361859.2		Q6IPX3

Frequencies

GnomAD3 genomes

AF:

0.000400

AC:

AN:

112618

Hom.:

Cov.:

AF XY:

0.000460

AC XY:

AN XY:

34786

show subpopulations

Gnomad AFR

AF:

0.0000646

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000931

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000365

Gnomad FIN

AF:

0.000323

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000732

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000385

AC:

AN:

174028

Hom.:

AF XY:

0.000246

AC XY:

AN XY:

61092

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000381

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000255

Gnomad NFE exome

AF:

0.000771

Gnomad OTH exome

AF:

0.000468

GnomAD4 exome

AF:

0.000492

AC:

538

AN:

1092526

Hom.:

Cov.:

AF XY:

0.000517

AC XY:

186

AN XY:

359620

show subpopulations

Gnomad4 AFR exome

AF:

0.0000388

Gnomad4 AMR exome

AF:

0.0000294

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000171

Gnomad4 FIN exome

AF:

0.000545

Gnomad4 NFE exome

AF:

0.000583

Gnomad4 OTH exome

AF:

0.000306

GnomAD4 genome

AF:

0.000400

AC:

AN:

112618

Hom.:

Cov.:

AF XY:

0.000460

AC XY:

AN XY:

34786

show subpopulations

Gnomad4 AFR

AF:

0.0000646

Gnomad4 AMR

AF:

0.0000931

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000365

Gnomad4 FIN

AF:

0.000323

Gnomad4 NFE

AF:

0.000732

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000564

Hom.:

Bravo

AF:

0.000431

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TCEAL6: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

4.2

DANN

Benign

0.61

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