Variant 2-32630653-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017735.5(TTC27):c.219G>C(p.Gln73His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,461,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

TTC27
NM_017735.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.22

Variant links:

Genes affected

TTC27 (HGNC:25986): (tetratricopeptide repeat domain 27)

TTC27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25071138).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC27	NM_017735.5 linkuse as main transcript	c.219G>C	p.Gln73His	missense_variant	2/20	ENST00000317907.9	NP_060205.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TTC27	ENST00000317907.9 linkuse as main transcript	c.219G>C	p.Gln73His	missense_variant	2/20	1	NM_017735.5	ENSP00000313953	P1
TTC27	ENST00000448773.5 linkuse as main transcript	c.69G>C	p.Gln23His	missense_variant	2/4	4		ENSP00000393327
TTC27	ENST00000647819.1 linkuse as main transcript	c.219G>C	p.Gln73His	missense_variant, NMD_transcript_variant	2/22			ENSP00000497009
TTC27	ENST00000454690.1 linkuse as main transcript	c.88+2273G>C		intron_variant, NMD_transcript_variant		3		ENSP00000392883

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250382

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135412

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000657

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1461186

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Jan 06, 2023

The c.219G>C (p.Q73H) alteration is located in exon 2 (coding exon 2) of the TTC27 gene. This alteration results from a G to C substitution at nucleotide position 219, causing the glutamine (Q) at amino acid position 73 to be replaced by a histidine (H). 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

0.19

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

.;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.7

.;M

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.12

Sift

Uncertain

0.014

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.81

.;P

Vest4

0.53

MutPred

0.38

.;Loss of stability (P = 0.1094);

MVP

0.77

MPC

0.042

ClinPred

0.45

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.13

gMVP

0.37

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