X-48893769-G-T

Position:

chrX-48893769-G-T

Variant summary

Our verdict is Benign. Variant got -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. 13/19 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein
TIMM17B	NM_001395498.1 linkuse as main transcript	c.479C>A	p.Thr160Asn	missense_variant	6/6	ENST00000696123.1	NP_001382427.1
TIMM17B	NM_001167947.2 linkuse as main transcript	c.629C>A	p.Thr210Asn	missense_variant	8/8		NP_001161419.1
TIMM17B	NM_001395497.1 linkuse as main transcript	c.629C>A	p.Thr210Asn	missense_variant	7/7		NP_001382426.1
TIMM17B	NM_005834.5 linkuse as main transcript	c.479C>A	p.Thr160Asn	missense_variant	7/7		NP_005825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMM17B	ENST00000696123.1 linkuse as main transcript	c.479C>A	p.Thr160Asn	missense_variant	6/6		NM_001395498.1	ENSP00000512416	P1	O60830-1

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

111792

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

AN XY:

33976

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

GnomAD3 exomes

AF:

0.000722

AC:

AN:

135666

Hom.:

AF XY:

0.00105

AC XY:

AN XY:

38966

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 SAS exome

AF:

0.00809

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

Gnomad4 AFR exome

AF:

0.0000394

Gnomad4 AMR exome

AF:

0.0000335

Gnomad4 ASJ exome

AF:

0.0000616

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00935

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000121

Gnomad4 OTH exome

AF:

0.000700

GnomAD4 genome

AF:

0.000277

AC:

AN:

111843

Hom.:

Cov.:

AF XY:

0.000206

AC XY:

AN XY:

34037

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00114

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00793

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000945

Gnomad4 OTH

AF:

0.00

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

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

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

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;.;.

MutationTaster

Benign

1.0

N;N

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

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.

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