chr2-32650179-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_017735.5(TTC27):​c.586C>T​(p.Leu196Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TTC27
NM_017735.5 missense

Scores

2
12
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31
Variant links:
Genes affected
TTC27 (HGNC:25986): (tetratricopeptide repeat domain 27)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.804

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TTC27NM_017735.5 linkc.586C>T p.Leu196Phe missense_variant Exon 5 of 20 ENST00000317907.9 NP_060205.3 Q6P3X3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TTC27ENST00000317907.9 linkc.586C>T p.Leu196Phe missense_variant Exon 5 of 20 1 NM_017735.5 ENSP00000313953.4 Q6P3X3
TTC27ENST00000647819.1 linkn.586C>T non_coding_transcript_exon_variant Exon 5 of 22 ENSP00000497009.1 A0A3B3IS02
TTC27ENST00000454690.1 linkn.88+21799C>T intron_variant Intron 1 of 3 3 ENSP00000392883.1 F8WCH1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152090
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461678
Hom.:
0
Cov.:
31
AF XY:
0.00000413
AC XY:
3
AN XY:
727144
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
AF:
0.00000658
AC:
1
AN:
152090
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
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
Bravo
AF:
0.0000113

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.586C>T (p.L196F) alteration is located in exon 5 (coding exon 5) of the TTC27 gene. This alteration results from a C to T substitution at nucleotide position 586, causing the leucine (L) at amino acid position 196 to be replaced by a phenylalanine (F). 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
Uncertain
0.37
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.050
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.58
D
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.53
FATHMM_MKL
Benign
0.63
D
LIST_S2
Uncertain
0.92
D
M_CAP
Benign
0.076
D
MetaRNN
Pathogenic
0.80
D
MetaSVM
Uncertain
0.040
D
MutationAssessor
Uncertain
2.9
M
PrimateAI
Uncertain
0.54
T
PROVEAN
Uncertain
-3.0
D
REVEL
Uncertain
0.56
Sift
Benign
0.099
T
Sift4G
Benign
0.14
T
Polyphen
1.0
D
Vest4
0.84
MutPred
0.53
Loss of helix (P = 0.0376);
MVP
0.92
MPC
0.23
ClinPred
0.96
D
GERP RS
4.3
Varity_R
0.25
gMVP
0.63

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.

Other links and lift over

dbSNP: rs1021156141; hg19: chr2-32875246; API