Variant 1-201965505-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The ENST00000367287.5(TIMM17A):c.392T>C(p.Ile131Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TIMM17A
ENST00000367287.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.96

Variant links:

Genes affected

TIMM17A (HGNC:17315): (translocase of inner mitochondrial membrane 17A) Predicted to contribute to protein transmembrane transporter activity. Predicted to be involved in protein import into mitochondrial matrix. Located in mitochondrial inner membrane and nucleoplasm. Is integral component of mitochondrial inner membrane. Part of TIM23 mitochondrial import inner membrane translocase complex. [provided by Alliance of Genome Resources, Apr 2022]

TIMM17A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.878

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMM17A	NM_006335.3 linkuse as main transcript	c.392T>C	p.Ile131Thr	missense_variant	5/6	ENST00000367287.5	NP_006326.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TIMM17A	ENST00000367287.5 linkuse as main transcript	c.392T>C	p.Ile131Thr	missense_variant	5/6	1	NM_006335.3	ENSP00000356256	P1
TIMM17A	ENST00000478378.5 linkuse as main transcript	n.534T>C		non_coding_transcript_exon_variant	6/7	3
TIMM17A	ENST00000482943.1 linkuse as main transcript	n.1602T>C		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461820

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 24, 2024

The c.392T>C (p.I131T) alteration is located in exon 5 (coding exon 5) of the TIMM17A gene. This alteration results from a T to C substitution at nucleotide position 392, causing the isoleucine (I) at amino acid position 131 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.22

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.054

MetaRNN

Pathogenic

0.88

MetaSVM

Benign

-0.47

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-4.7

REVEL

Uncertain

0.48

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.94

MutPred

0.64

Loss of stability (P = 0.0038);

MVP

0.53

MPC

1.2

ClinPred

1.0

GERP RS

5.1

Varity_R

0.68

gMVP

0.88

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over