Variant 9-127724224-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_144965.3(TTC16):c.977C>T(p.Ala326Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,613,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

TTC16
NM_144965.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.64

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC16	NM_144965.3 link	c.977C>T	p.Ala326Val	missense_variant	8/14	ENST00000373289.4	NP_659402.1	Q8NEE8-1B4DH05

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC16	ENST00000373289.4 link	c.977C>T	p.Ala326Val	missense_variant	8/14	1	NM_144965.3	ENSP00000362386.3		Q8NEE8-1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000361

AC:

AN:

249542

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135442

show subpopulations

Gnomad AFR exome

AF:

0.000559

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1460696

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726654

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000164

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000277

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000577

AC:

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

Feb 27, 2024

The c.977C>T (p.A326V) alteration is located in exon 8 (coding exon 8) of the TTC16 gene. This alteration results from a C to T substitution at nucleotide position 977, causing the alanine (A) at amino acid position 326 to be replaced by a valine (V). 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

0.13

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.070

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.67

M_CAP

Benign

0.022

MetaRNN

Benign

0.066

MetaSVM

Benign

-0.65

MutationAssessor

Uncertain

2.0

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.18

Sift

Benign

0.083

Sift4G

Uncertain

0.0050

Polyphen

0.90

Vest4

0.14

MVP

0.58

MPC

0.38

ClinPred

0.16

GERP RS

3.7

Varity_R

0.15

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.42

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.42

Position offset: -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