Variant 9-127720334-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000373289.4(TTC16):c.596A>T(p.Gln199Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000341 in 1,613,322 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 3 hom. )

Consequence

TTC16
ENST00000373289.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.335

Variant links:

Genes affected

TTC16 (HGNC:26536): (tetratricopeptide repeat domain 16)

TTC16 links:

PTRH1 (HGNC:27039): (peptidyl-tRNA hydrolase 1 homolog) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PTRH1 links:

TTC16 (HGNC:):

TTC16 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016613662).

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC16	NM_144965.3 linkuse as main transcript	c.596A>T	p.Gln199Leu	missense_variant	6/14	ENST00000373289.4	NP_659402.1	Q8NEE8-1B4DH05

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC16	ENST00000373289.4 linkuse as main transcript	c.596A>T	p.Gln199Leu	missense_variant	6/14	1	NM_144965.3	ENSP00000362386.3		Q8NEE8-1

Frequencies

GnomAD3 genomes

AF:

0.000309

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.000851

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000382

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000306

AC:

AN:

251224

Hom.:

AF XY:

0.000375

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.000299

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000344

AC:

503

AN:

1461128

Hom.:

Cov.:

AF XY:

0.000378

AC XY:

275

AN XY:

726864

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00107

Gnomad4 FIN exome

AF:

0.000549

Gnomad4 NFE exome

AF:

0.000315

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000309

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000349

AC XY:

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.000851

Gnomad4 NFE

AF:

0.000383

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000223

Hom.:

Bravo

AF:

0.000317

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000362

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2022

The c.596A>T (p.Q199L) alteration is located in exon 6 (coding exon 6) of the TTC16 gene. This alteration results from a A to T substitution at nucleotide position 596, causing the glutamine (Q) at amino acid position 199 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.1

DANN

Benign

0.77

DEOGEN2

Benign

0.038

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.046

LIST_S2

Benign

0.36

M_CAP

Benign

0.0048

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.24

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.046

Sift

Benign

0.34

Sift4G

Benign

0.20

Polyphen

0.0030

Vest4

0.27

MVP

0.47

MPC

0.15

ClinPred

0.027

GERP RS

-1.8

Varity_R

0.069

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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