NM_001395498.1:c.479C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001395498.1(TIMM17B):c.479C>A(p.Thr160Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000528 in 1,167,910 control chromosomes in the GnomAD database, including 4 homozygotes. There are 313 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., 7 hem., cov: 23)

Exomes 𝑓: 0.00055 ( 4 hom. 306 hem. )

Consequence

TIMM17B
NM_001395498.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.04

Publications

0 publications found

Variant links:

Genes affected

TIMM17B (HGNC:17310): (translocase of inner mitochondrial membrane 17B) This gene encodes a multipass transmembrane protein that forms an integral component of the mitochondrial translocase TIM23 complex. This complex facilitates the transport of mitochondrial proteins from the cytosol across the mitochondrial inner membrane and into the mitochondrion. There is a pseudogene for this gene on chromosome 12. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

TIMM17B links:

PQBP1 (HGNC:9330): (polyglutamine binding protein 1) This gene encodes a nuclear polyglutamine-binding protein that is involved with transcription activation. The encoded protein contains a WW domain. Mutations in this gene have been found in patients with Renpenning syndrome 1 and other syndromes with X-linked cognitive disability. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.[provided by RefSeq, Nov 2009]

PQBP1 Gene-Disease associations (from GenCC):

Renpenning syndrome
Inheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, ClinGen
hamel cerebro-palato-cardiac syndrome
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
X-linked intellectual disability, Golabi-Ito-hall type
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
X-linked intellectual disability, Porteous type
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
X-linked intellectual disability, Sutherland-Haan type
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

PQBP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004162401).

BP6

Variant X-48893769-G-T is Benign according to our data. Variant chrX-48893769-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2660480.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
TIMM17B	NM_001395498.1 link	c.479C>A	p.Thr160Asn	missense_variant	Exon 6 of 6	ENST00000696123.1	NP_001382427.1
TIMM17B	NM_001167947.2 link	c.629C>A	p.Thr210Asn	missense_variant	Exon 8 of 8		NP_001161419.1
TIMM17B	NM_001395497.1 link	c.629C>A	p.Thr210Asn	missense_variant	Exon 7 of 7		NP_001382426.1
TIMM17B	NM_005834.5 link	c.479C>A	p.Thr160Asn	missense_variant	Exon 7 of 7		NP_005825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMM17B	ENST00000696123.1 link	c.479C>A	p.Thr160Asn	missense_variant	Exon 6 of 6		NM_001395498.1	ENSP00000512416.1		O60830-1

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

111792

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00114

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00791

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00837

Gnomad NFE

AF:

0.0000945

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000722

AC:

AN:

135666

AF XY:

0.00105

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000471

Gnomad ASJ exome

AF:

0.000271

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000555

AC:

586

AN:

1056067

Hom.:

Cov.:

AF XY:

0.000903

AC XY:

306

AN XY:

338923

show subpopulations

African (AFR)

AF:

0.0000394

AC:

AN:

25411

American (AMR)

AF:

0.0000335

AC:

AN:

29840

Ashkenazi Jewish (ASJ)

AF:

0.0000616

AC:

AN:

16233

East Asian (EAS)

AF:

0.00

AC:

AN:

29799

South Asian (SAS)

AF:

0.00935

AC:

442

AN:

47281

European-Finnish (FIN)

AF:

0.00

AC:

AN:

38528

Middle Eastern (MID)

AF:

0.00283

AC:

AN:

3892

European-Non Finnish (NFE)

AF:

0.000121

AC:

AN:

820827

Other (OTH)

AF:

0.000700

AC:

AN:

44256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000277

AC:

AN:

111843

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

AN XY:

34037

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30884

American (AMR)

AF:

0.00

AC:

AN:

10650

Ashkenazi Jewish (ASJ)

AF:

0.00114

AC:

AN:

2631

East Asian (EAS)

AF:

0.00

AC:

AN:

3533

South Asian (SAS)

AF:

0.00793

AC:

AN:

2648

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6175

Middle Eastern (MID)

AF:

0.00917

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.0000945

AC:

AN:

52902

Other (OTH)

AF:

0.00

AC:

AN:

1518

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.00125

AC:

150

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TIMM17B: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.92

CADD

Benign

7.4

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.023

.;T;.;T

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.72

.;T;T;T

MetaRNN

Benign

0.0042

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.76

.;N;.;.

PhyloP100

2.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.10

.;N;N;.

REVEL

Benign

0.057

Sift

Benign

0.58

.;T;T;.

Sift4G

Benign

0.48

T;T;T;T

Polyphen

0.0040

.;B;.;.

Vest4

0.11

MutPred

0.21

.;Loss of phosphorylation at T160 (P = 0.0013);.;.;

MVP

0.18

MPC

0.48

ClinPred

0.011

GERP RS

3.2

Varity_R

0.046

gMVP

0.44

Mutation Taster

=99/1

polymorphism (auto)

(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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NM_001395498.1:c.479C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over