Genetic Variant TTC17:p.Thr451Ser (chr11-43404016-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018259.6(TTC17):c.1351A>T(p.Thr451Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000482 in 1,452,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T451I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TTC17
NM_018259.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.50

Publications

0 publications found

Variant links:

Genes affected

TTC17 (HGNC:25596): (tetratricopeptide repeat domain 17) Involved in actin filament polymerization and cilium organization. Located in actin cytoskeleton; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

TTC17 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09713817).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018259.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC17	NM_018259.6	MANE Select	c.1351A>T	p.Thr451Ser	missense	Exon 11 of 24	NP_060729.2
TTC17	NM_001376525.1		c.1351A>T	p.Thr451Ser	missense	Exon 11 of 25	NP_001363454.1	A0A994J3X0
TTC17	NM_001376526.1		c.1261A>T	p.Thr421Ser	missense	Exon 10 of 23	NP_001363455.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC17	ENST00000039989.9	TSL:1 MANE Select	c.1351A>T	p.Thr451Ser	missense	Exon 11 of 24	ENSP00000039989.4	Q96AE7-1
TTC17	ENST00000299240.10	TSL:1	c.1351A>T	p.Thr451Ser	missense	Exon 11 of 20	ENSP00000299240.5	Q96AE7-2
TTC17	ENST00000526774.5	TSL:1	n.1261A>T		non_coding_transcript_exon	Exon 6 of 15

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000482

AC:

AN:

1452250

Hom.:

Cov.:

AF XY:

0.00000693

AC XY:

AN XY:

721994

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32952

American (AMR)

AF:

0.00

AC:

AN:

42916

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25776

East Asian (EAS)

AF:

0.00

AC:

AN:

39264

South Asian (SAS)

AF:

0.00

AC:

AN:

84138

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00000632

AC:

AN:

1108278

Other (OTH)

AF:

0.00

AC:

AN:

60002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.018

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.78

M_CAP

Benign

0.0061

MetaRNN

Benign

0.097

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

3.5

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.53

REVEL

Benign

0.057

Sift

Benign

0.19

Sift4G

Benign

0.27

Polyphen

0.41

Vest4

0.34

MutPred

0.24

Gain of phosphorylation at T451 (P = 0.043)

MVP

0.19

MPC

0.22

ClinPred

0.54

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.040

gMVP

0.30

Mutation Taster

=85/15

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over