dbSNP rs139319173: TIMM29:p.Asp225Asn (chr19-10929592-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138358.4(TIMM29):c.673G>A(p.Asp225Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00132 in 1,613,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 0 hom. )

Consequence

TIMM29
NM_138358.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.44

Variant links:

Genes affected

TIMM29 (HGNC:25152): (translocase of inner mitochondrial membrane 29) Enables protein transporter activity. Involved in protein insertion into mitochondrial inner membrane. Located in mitochondrial inner membrane and mitochondrial intermembrane space. Part of TIM22 mitochondrial import inner membrane insertion complex. [provided by Alliance of Genome Resources, Apr 2022]

TIMM29 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026783824).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMM29	NM_138358.4 link	c.673G>A	p.Asp225Asn	missense_variant	Exon 2 of 2	ENST00000270502.7	NP_612367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMM29	ENST00000270502.7 link	c.673G>A	p.Asp225Asn	missense_variant	Exon 2 of 2	1	NM_138358.4	ENSP00000270502.5		Q9BSF4
TIMM29	ENST00000588807.1 link	n.-30G>A		upstream_gene_variant		5		ENSP00000466926.1		K7ENF5

Frequencies

GnomAD3 genomes

AF:

0.000907

AC:

138

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00173

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000806

AC:

200

AN:

248080

Hom.:

AF XY:

0.000836

AC XY:

113

AN XY:

135164

show subpopulations

Gnomad AFR exome

AF:

0.000510

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00151

Gnomad OTH exome

AF:

0.000329

GnomAD4 exome

AF:

0.00136

AC:

1984

AN:

1460742

Hom.:

Cov.:

AF XY:

0.00131

AC XY:

955

AN XY:

726674

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000229

Gnomad4 NFE exome

AF:

0.00168

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.000906

AC:

138

AN:

152344

Hom.:

Cov.:

AF XY:

0.000832

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00173

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00117

Hom.:

Bravo

AF:

0.000986

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.000583

AC:

ExAC

AF:

0.000701

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00142

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 22, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.673G>A (p.D225N) alteration is located in exon 2 (coding exon 2) of the C19orf52 gene. This alteration results from a G to A substitution at nucleotide position 673, causing the aspartic acid (D) at amino acid position 225 to be replaced by an asparagine (N). 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

Benign

0.22

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0096

Eigen

Benign

0.10

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.80

M_CAP

Benign

0.010

MetaRNN

Benign

0.027

MetaSVM

Benign

-0.91

PROVEAN

Benign

-1.0

REVEL

Benign

0.12

Sift

Uncertain

0.0060

Sift4G

Benign

0.10

Polyphen

0.92

Vest4

0.21

MVP

0.085

MPC

1.0

ClinPred

0.024

GERP RS

4.9

Varity_R

0.38

gMVP

0.38

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