Variant chr6-44282478-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_182539.4(TCTE1):c.928G>A(p.Glu310Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,611,492 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 2 hom. )

Consequence

TCTE1
NM_182539.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.466

Variant links:

Genes affected

TCTE1 (HGNC:11693): (t-complex-associated-testis-expressed 1) Predicted to be involved in flagellated sperm motility. Predicted to be located in sperm flagellum. [provided by Alliance of Genome Resources, Apr 2022]

TCTE1 links:

POLR1C (HGNC:):

POLR1C links:

TMEM151B (HGNC:21315): (transmembrane protein 151B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM151B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007897109).

BP6

Variant 6-44282478-C-T is Benign according to our data. Variant chr6-44282478-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3043501.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 224 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCTE1	NM_182539.4 linkuse as main transcript	c.928G>A	p.Glu310Lys	missense_variant	4/5	ENST00000371505.5	NP_872345.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCTE1	ENST00000371505.5 linkuse as main transcript	c.928G>A	p.Glu310Lys	missense_variant	4/5	1	NM_182539.4	ENSP00000360560	P1
TCTE1	ENST00000371504.1 linkuse as main transcript	c.388-2088G>A		intron_variant		3		ENSP00000360559
TMEM151B	ENST00000438774.2 linkuse as main transcript	c.576+8972C>T		intron_variant		3		ENSP00000409337		Q8IW70-2

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

224

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00253

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00166

AC:

412

AN:

248786

Hom.:

AF XY:

0.00171

AC XY:

230

AN XY:

134566

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00163

Gnomad FIN exome

AF:

0.000310

Gnomad NFE exome

AF:

0.00263

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00248

AC:

3622

AN:

1459162

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

1812

AN XY:

725912

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00161

Gnomad4 FIN exome

AF:

0.000197

Gnomad4 NFE exome

AF:

0.00297

Gnomad4 OTH exome

AF:

0.00176

GnomAD4 genome

AF:

0.00147

AC:

224

AN:

152330

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.000649

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00253

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00246

Hom.:

Bravo

AF:

0.00152

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00384

AC:

ExAC

AF:

0.00159

AC:

193

EpiCase

AF:

0.00224

EpiControl

AF:

0.00231

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TCTE1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 16, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.80

DEOGEN2

Benign

0.0050

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.065

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.014

MetaRNN

Benign

0.0079

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.86

REVEL

Benign

0.054

Sift

Benign

0.75

Sift4G

Benign

0.82

Polyphen

0.68

Vest4

0.16

MVP

0.014

MPC

0.42

ClinPred

0.0097

GERP RS

2.5

Varity_R

0.089

gMVP

0.47

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