Genetic Variant NM_006335.3:c.21G>C (chr1-201955547-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006335.3(TIMM17A):c.21G>C(p.Glu7Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E7G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

TIMM17A
NM_006335.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0160

Publications

0 publications found

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 was made for transcript

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=0.19666943).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006335.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMM17A	NM_006335.3	MANE Select	c.21G>C	p.Glu7Asp	missense	Exon 1 of 6	NP_006326.1	Q99595

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TIMM17A	ENST00000367287.5	TSL:1 MANE Select	c.21G>C	p.Glu7Asp	missense	Exon 1 of 6	ENSP00000356256.4	Q99595
TIMM17A	ENST00000955674.1		c.21G>C	p.Glu7Asp	missense	Exon 1 of 7	ENSP00000625733.1
TIMM17A	ENST00000934114.1		c.21G>C	p.Glu7Asp	missense	Exon 1 of 6	ENSP00000604173.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251454

AF XY:

0.00

show subpopulations

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000207

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.049

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.82

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.074

MetaRNN

Benign

0.20

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

0.016

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-2.2

REVEL

Benign

0.22

Sift

Benign

0.36

Sift4G

Benign

0.36

Polyphen

0.019

Vest4

0.58

MutPred

0.57

Loss of phosphorylation at Y4 (P = 0.1211)

MVP

0.29

MPC

1.0

ClinPred

0.37

GERP RS

-1.1

PromoterAI

-0.031

Neutral

(source)

Varity_R

0.22

gMVP

0.85

Mutation Taster

=49/51

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over