Genetic Variant NM_018259.6:c.239A>G (chr11-43379312-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018259.6(TTC17):c.239A>G(p.Lys80Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000627 in 1,611,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

TTC17
NM_018259.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73

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:

ENSG00000255340 (HGNC:):

ENSG00000255340 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.121260494).

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.239A>G	p.Lys80Arg	missense	Exon 2 of 24	NP_060729.2
TTC17	NM_001376525.1		c.239A>G	p.Lys80Arg	missense	Exon 2 of 25	NP_001363454.1	A0A994J3X0
TTC17	NM_001376527.1		c.239A>G	p.Lys80Arg	missense	Exon 2 of 21	NP_001363456.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TTC17	ENST00000039989.9	TSL:1 MANE Select	c.239A>G	p.Lys80Arg	missense	Exon 2 of 24	ENSP00000039989.4	Q96AE7-1
TTC17	ENST00000299240.10	TSL:1	c.239A>G	p.Lys80Arg	missense	Exon 2 of 20	ENSP00000299240.5	Q96AE7-2
TTC17	ENST00000867749.1		c.239A>G	p.Lys80Arg	missense	Exon 2 of 25	ENSP00000537808.1

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000807

AC:

AN:

247696

AF XY:

0.0000895

show subpopulations

Gnomad AFR exome

AF:

0.0000623

Gnomad AMR exome

AF:

0.000211

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000569

AC:

AN:

1459356

Hom.:

Cov.:

AF XY:

0.0000510

AC XY:

AN XY:

726030

show subpopulations

African (AFR)

AF:

0.0000600

AC:

AN:

33356

American (AMR)

AF:

0.000204

AC:

AN:

44132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39496

South Asian (SAS)

AF:

0.000222

AC:

AN:

85714

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

1111186

Other (OTH)

AF:

0.0000332

AC:

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

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

AF:

0.000118

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41456

American (AMR)

AF:

0.000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.000207

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000141

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000824

AC:

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

0.10

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.030

Eigen

Benign

-0.061

Eigen_PC

Benign

0.070

FATHMM_MKL

Uncertain

0.83

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.011

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

2.7

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.98

REVEL

Benign

0.091

Sift

Benign

0.091

Sift4G

Benign

0.23

Polyphen

0.0030

Vest4

0.26

MVP

0.27

MPC

0.16

ClinPred

0.051

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.12

gMVP

0.44

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over