X-48893905-C-A

Variant names:

• chrX-48893905-C-A
• rs782047781
• NM_001395498.1:c.425G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001395498.1(TIMM17B):​c.425G>T​(p.Arg142Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: TIMM17B NM_001395498.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.80

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25019893).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMM17B	NM_001395498.1	c.425G>T	p.Arg142Leu	missense_variant	Exon 5 of 6	ENST00000696123.1	NP_001382427.1
TIMM17B	NM_001167947.2	c.575G>T	p.Arg192Leu	missense_variant	Exon 7 of 8		NP_001161419.1
TIMM17B	NM_001395497.1	c.575G>T	p.Arg192Leu	missense_variant	Exon 6 of 7		NP_001382426.1
TIMM17B	NM_005834.5	c.425G>T	p.Arg142Leu	missense_variant	Exon 6 of 7		NP_005825.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMM17B	ENST00000696123.1	c.425G>T	p.Arg142Leu	missense_variant	Exon 5 of 6		NM_001395498.1	ENSP00000512416.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.34
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	.;T;.;T
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.18	.;T;T;T
M_CAP	Uncertain	0.21	D
MetaRNN	Benign	0.25	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;L;.;.
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-4.7	.;D;D;.
REVEL	Benign	0.072
Sift	Benign	0.099	.;T;D;.
Sift4G	Benign	0.11	T;T;T;T
Polyphen		0.093	.;B;.;.
Vest4		0.43
MutPred		0.42		.;Loss of disorder (P = 0.0722);.;.;
MVP		0.082
MPC		0.79
ClinPred		0.97	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.35
gMVP		0.66

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

Other links and lift over

dbSNP: rs782047781; hg19: chrX-48751188;