Genetic Variant NM_032174.6:c.-114A>C (chr1-161226376-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032174.6(TOMM40L):c.-114A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 869,156 control chromosomes in the GnomAD database, including 52,557 homozygotes. 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: 𝑓 0.29 ( 7165 hom., cov: 27)

Exomes 𝑓: 0.35 ( 45392 hom. )

Consequence

TOMM40L
NM_032174.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.90

Publications

16 publications found

Variant links:

Genes affected

TOMM40L (HGNC:25756): (translocase of outer mitochondrial membrane 40 like) Predicted to enable protein transmembrane transporter activity. Predicted to be involved in protein import into mitochondrial matrix. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

TOMM40L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032174.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TOMM40L	NM_032174.6	MANE Select	c.-114A>C	5_prime_UTR	Exon 2 of 10	NP_115550.2
TOMM40L	NM_001286373.2		c.-114A>C	5_prime_UTR	Exon 2 of 9	NP_001273302.1
TOMM40L	NM_001286374.2		c.-114A>C	5_prime_UTR	Exon 2 of 8	NP_001273303.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
TOMM40L	ENST00000367988.8	TSL:2 MANE Select	c.-114A>C	5_prime_UTR	Exon 2 of 10	ENSP00000356967.3
TOMM40L	ENST00000367987.1	TSL:1	c.-114A>C	5_prime_UTR	Exon 1 of 9	ENSP00000356966.1
TOMM40L	ENST00000465512.5	TSL:2	n.86A>C	non_coding_transcript_exon	Exon 2 of 6

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43297

AN:

150096

Hom.:

7165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.122

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.356

Gnomad ASJ

AF:

0.312

Gnomad EAS

AF:

0.535

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.319

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.308

GnomAD4 exome

AF:

0.349

AC:

250592

AN:

718940

Hom.:

45392

Cov.:

AF XY:

0.347

AC XY:

127073

AN XY:

366192

show subpopulations

African (AFR)

AF:

0.117

AC:

2060

AN:

17566

American (AMR)

AF:

0.397

AC:

9248

AN:

23318

Ashkenazi Jewish (ASJ)

AF:

0.326

AC:

5274

AN:

16178

East Asian (EAS)

AF:

0.535

AC:

17192

AN:

32116

South Asian (SAS)

AF:

0.318

AC:

17266

AN:

54312

European-Finnish (FIN)

AF:

0.315

AC:

12318

AN:

39150

Middle Eastern (MID)

AF:

0.324

AC:

828

AN:

2558

European-Non Finnish (NFE)

AF:

0.350

AC:

174607

AN:

499184

Other (OTH)

AF:

0.341

AC:

11799

AN:

34558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

8088

16176

24265

32353

40441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4004

8008

12012

16016

20020

<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

AF:

0.288

AC:

43304

AN:

150216

Hom.:

7165

Cov.:

AF XY:

0.289

AC XY:

21206

AN XY:

73272

show subpopulations

African (AFR)

AF:

0.122

AC:

4969

AN:

40860

American (AMR)

AF:

0.357

AC:

5386

AN:

15098

Ashkenazi Jewish (ASJ)

AF:

0.312

AC:

1078

AN:

3460

East Asian (EAS)

AF:

0.535

AC:

2661

AN:

4978

South Asian (SAS)

AF:

0.313

AC:

1473

AN:

4710

European-Finnish (FIN)

AF:

0.319

AC:

3290

AN:

10318

Middle Eastern (MID)

AF:

0.276

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.347

AC:

23438

AN:

67508

Other (OTH)

AF:

0.306

AC:

639

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1430

2860

4291

5721

7151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.332

Hom.:

25337

Bravo

AF:

0.286

Asia WGS

AF:

0.434

AC:

1505

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

1.9

PromoterAI

-0.016

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over