rs782624478

Variant names:

• chrX-48893769-G-A
• rs782624478
• NM_001395498.1:c.479C>T

Your query was ambiguous. Multiple possible variants found:

• chrX-48893769-G-A
• chrX-48893769-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395498.1(TIMM17B):​c.479C>T​(p.Thr160Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000947 in 1,056,070 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T160N) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.5e-7 (0 hom. 0 hem.)
• Consequence: TIMM17B NM_001395498.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 0 publications found

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]

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

ACMG classification

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=0.0834471).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMM17B	NM_001395498.1	c.479C>T	p.Thr160Ile	missense_variant	Exon 6 of 6	ENST00000696123.1	NP_001382427.1
TIMM17B	NM_001167947.2	c.629C>T	p.Thr210Ile	missense_variant	Exon 8 of 8		NP_001161419.1
TIMM17B	NM_001395497.1	c.629C>T	p.Thr210Ile	missense_variant	Exon 7 of 7		NP_001382426.1
TIMM17B	NM_005834.5	c.479C>T	p.Thr160Ile	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	c.479C>T	p.Thr160Ile	missense_variant	Exon 6 of 6		NM_001395498.1	ENSP00000512416.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00 AC: 0 AN: 135666 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 9.47e-7 AC: 1 AN: 1056070 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 338926

African (AFR) AF: 0.0000394 AC: 1 AN: 25411

American (AMR) AF: 0.00 AC: 0 AN: 29840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16233

East Asian (EAS) AF: 0.00 AC: 0 AN: 29799

South Asian (SAS) AF: 0.00 AC: 0 AN: 47282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38528

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3892

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 820829

Other (OTH) AF: 0.00 AC: 0 AN: 44256

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.92
DEOGEN2	Benign	0.062	.;T;.;T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.81	.;T;T;T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.083	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;L;.;.
PhyloP100		2.0
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	.;N;N;.
REVEL	Benign	0.059
Sift	Benign	0.19	.;T;T;.
Sift4G	Benign	0.17	T;T;T;T
Polyphen		0.0080	.;B;.;.
Vest4		0.14
MutPred		0.24		.;Loss of phosphorylation at T160 (P = 0.0013);.;.;
MVP		0.11
MPC		0.59
ClinPred		0.046	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.55
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs782624478; hg19: chrX-48751052;