Variant chr2-32633976-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_017735.5(TTC27):c.367T>C(p.Ser123Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,422 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TTC27
NM_017735.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.10

Variant links:

Genes affected

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

TTC27 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02600804).

BP6

Variant 2-32633976-T-C is Benign according to our data. Variant chr2-32633976-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3184208.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC27	NM_017735.5 linkuse as main transcript	c.367T>C	p.Ser123Pro	missense_variant	3/20	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.367T>C	p.Ser123Pro	missense_variant	3/20	1	NM_017735.5	ENSP00000313953	P1
TTC27	ENST00000448773.5 linkuse as main transcript	c.217T>C	p.Ser73Pro	missense_variant	3/4	4		ENSP00000393327
TTC27	ENST00000647819.1 linkuse as main transcript	c.367T>C	p.Ser123Pro	missense_variant, NMD_transcript_variant	3/22			ENSP00000497009
TTC27	ENST00000454690.1 linkuse as main transcript	c.88+5596T>C		intron_variant, NMD_transcript_variant		3		ENSP00000392883

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461422

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727010

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.040

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.066

.;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.026

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-2.9

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

3.2

N;N

REVEL

Benign

0.063

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

.;B

Vest4

0.25

MutPred

0.45

.;Gain of loop (P = 0.0045);

MVP

0.29

MPC

0.046

ClinPred

0.047

GERP RS

2.7

Varity_R

0.050

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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