Variant 3-39110854-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001366900.1(TTC21A):c.272G>A(p.Arg91Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,613,108 control chromosomes in the GnomAD database, including 67,845 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.34 ( 9932 hom., cov: 33)

Exomes 𝑓: 0.28 ( 57913 hom. )

Consequence

TTC21A
NM_001366900.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.675

Variant links:

Genes affected

TTC21A (HGNC:30761): (tetratricopeptide repeat domain 21A) Involved in flagellated sperm motility and spermatid development. Predicted to be located in cilium. Predicted to be part of intraciliary transport particle A. Implicated in spermatogenic failure 37. [provided by Alliance of Genome Resources, Apr 2022]

TTC21A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0523174E-4).

BP6

Variant 3-39110854-G-A is Benign according to our data. Variant chr3-39110854-G-A is described in ClinVar as [Benign]. Clinvar id is 3060399.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC21A	NM_001366900.1 linkuse as main transcript	c.272G>A	p.Arg91Gln	missense_variant	4/29	ENST00000683103.1	NP_001353829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC21A	ENST00000683103.1 linkuse as main transcript	c.272G>A	p.Arg91Gln	missense_variant	4/29		NM_001366900.1	ENSP00000507739	P1

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52280

AN:

152020

Hom.:

9929

Cov.:

show subpopulations

Gnomad AFR

AF:

0.515

Gnomad AMI

AF:

0.213

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.355

Gnomad EAS

AF:

0.265

Gnomad SAS

AF:

0.263

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.361

Gnomad NFE

AF:

0.278

Gnomad OTH

AF:

0.335

GnomAD3 exomes

AF:

0.289

AC:

71842

AN:

248984

Hom.:

10913

AF XY:

0.285

AC XY:

38576

AN XY:

135150

show subpopulations

Gnomad AFR exome

AF:

0.522

Gnomad AMR exome

AF:

0.264

Gnomad ASJ exome

AF:

0.353

Gnomad EAS exome

AF:

0.243

Gnomad SAS exome

AF:

0.279

Gnomad FIN exome

AF:

0.257

Gnomad NFE exome

AF:

0.274

Gnomad OTH exome

AF:

0.294

GnomAD4 exome

AF:

0.278

AC:

405757

AN:

1460970

Hom.:

57913

Cov.:

AF XY:

0.277

AC XY:

201325

AN XY:

726808

show subpopulations

Gnomad4 AFR exome

AF:

0.518

Gnomad4 AMR exome

AF:

0.270

Gnomad4 ASJ exome

AF:

0.357

Gnomad4 EAS exome

AF:

0.274

Gnomad4 SAS exome

AF:

0.274

Gnomad4 FIN exome

AF:

0.259

Gnomad4 NFE exome

AF:

0.269

Gnomad4 OTH exome

AF:

0.290

GnomAD4 genome

AF:

0.344

AC:

52332

AN:

152138

Hom.:

9932

Cov.:

AF XY:

0.340

AC XY:

25320

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.515

Gnomad4 AMR

AF:

0.286

Gnomad4 ASJ

AF:

0.355

Gnomad4 EAS

AF:

0.265

Gnomad4 SAS

AF:

0.264

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.278

Gnomad4 OTH

AF:

0.335

Alfa

AF:

0.287

Hom.:

16664

Bravo

AF:

0.355

TwinsUK

AF:

0.274

AC:

1016

ALSPAC

AF:

0.285

AC:

1097

ESP6500AA

AF:

0.492

AC:

1928

ESP6500EA

AF:

0.285

AC:

2377

ExAC

AF:

0.291

AC:

35236

Asia WGS

AF:

0.309

AC:

1072

AN:

3478

EpiCase

AF:

0.276

EpiControl

AF:

0.273

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TTC21A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 2019

This variant is classified as 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

0.074

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.015

T;.

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.80

T;T

MetaRNN

Benign

0.00011

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.18

PROVEAN

Uncertain

-2.5

N;N

REVEL

Benign

0.13

Sift

Benign

0.11

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.070

B;B

Vest4

0.068

MPC

0.16

ClinPred

0.0099

GERP RS

0.56

Varity_R

0.073

gMVP

0.082

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