Variant 3-39109123-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001366900.1(TTC21A):c.66C>T(p.His22His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,614,142 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00096 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 4 hom. )

Consequence

TTC21A
NM_001366900.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.382

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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 3-39109123-C-T is Benign according to our data. Variant chr3-39109123-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3388204.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.382 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000958 (146/152338) while in subpopulation AMR AF= 0.00242 (37/15306). AF 95% confidence interval is 0.0018. There are 0 homozygotes in gnomad4. There are 73 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC21A	NM_001366900.1 link	c.66C>T	p.His22His	synonymous_variant	Exon 2 of 29	ENST00000683103.1	NP_001353829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC21A	ENST00000683103.1 link	c.66C>T	p.His22His	synonymous_variant	Exon 2 of 29		NM_001366900.1	ENSP00000507739.1		A0A804HK20

Frequencies

GnomAD3 genomes

AF:

0.000959

AC:

146

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00143

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000886

AC:

221

AN:

249566

Hom.:

AF XY:

0.000901

AC XY:

122

AN XY:

135398

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.00232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00110

Gnomad OTH exome

AF:

0.00215

GnomAD4 exome

AF:

0.00101

AC:

1476

AN:

1461804

Hom.:

Cov.:

AF XY:

0.000985

AC XY:

716

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00233

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.00116

Gnomad4 OTH exome

AF:

0.00106

GnomAD4 genome

AF:

0.000958

AC:

146

AN:

152338

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00143

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.00119

EpiCase

AF:

0.00153

EpiControl

AF:

0.00113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TTC21A: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.4

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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