Variant chr14-20295416-G-A 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_138376.3(TTC5):c.954C>T(p.Thr318Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00368 in 1,614,118 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 17 hom. )

Consequence

TTC5
NM_138376.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.801

Variant links:

Genes affected

TTC5 (HGNC:19274): (tetratricopeptide repeat domain 5) Predicted to enable DNA binding activity and chromatin binding activity. Predicted to be involved in DNA repair. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TTC5 links:

TTC5 (HGNC:):

TTC5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 14-20295416-G-A is Benign according to our data. Variant chr14-20295416-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2644040.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.801 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00217 (331/152224) while in subpopulation NFE AF= 0.0039 (265/68002). AF 95% confidence interval is 0.00351. There are 2 homozygotes in gnomad4. There are 143 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC5	NM_138376.3 linkuse as main transcript	c.954C>T	p.Thr318Thr	synonymous_variant	8/10	ENST00000258821.8	NP_612385.2	Q8N0Z6Q86T04

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TTC5	ENST00000258821.8 linkuse as main transcript	c.954C>T	p.Thr318Thr	synonymous_variant	8/10	1	NM_138376.3	ENSP00000258821.3	Q8N0Z6
TTC5	ENST00000383029.7 linkuse as main transcript	n.*499C>T		non_coding_transcript_exon_variant	8/10	1		ENSP00000372496.3	H9KV81
TTC5	ENST00000383029.7 linkuse as main transcript	n.*499C>T		3_prime_UTR_variant	8/10	1		ENSP00000372496.3	H9KV81
TTC5	ENST00000554157.5 linkuse as main transcript	n.965C>T		non_coding_transcript_exon_variant	8/9	2

Frequencies

GnomAD3 genomes

AF:

0.00218

AC:

331

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00390

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00191

AC:

481

AN:

251388

Hom.:

AF XY:

0.00197

AC XY:

267

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00162

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000870

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00310

Gnomad OTH exome

AF:

0.00244

GnomAD4 exome

AF:

0.00383

AC:

5606

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00373

AC XY:

2710

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00183

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000403

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.00476

Gnomad4 OTH exome

AF:

0.00242

GnomAD4 genome

AF:

0.00217

AC:

331

AN:

152224

Hom.:

Cov.:

AF XY:

0.00192

AC XY:

143

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00390

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00284

Hom.:

Bravo

AF:

0.00227

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2024

TTC5: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.8

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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