rs10826178

Variant summary

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

The NM_003201.3(TFAM):​c.221-680G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 152,086 control chromosomes in the GnomAD database, including 23,020 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 0.53 ( 23020 hom., cov: 32)

Consequence

TFAM
NM_003201.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.869

Publications

8 publications found
Variant links:
Genes affected
TFAM (HGNC:11741): (transcription factor A, mitochondrial) This gene encodes a key mitochondrial transcription factor containing two high mobility group motifs. The encoded protein also functions in mitochondrial DNA replication and repair. Sequence polymorphisms in this gene are associated with Alzheimer's and Parkinson's diseases. There are pseudogenes for this gene on chromosomes 6, 7, and 11. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]
TFAM Gene-Disease associations (from GenCC):
  • mitochondrial DNA depletion syndrome 15 (hepatocerebral type)
    Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

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=-0.9).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TFAMNM_003201.3 linkc.221-680G>A intron_variant Intron 2 of 6 ENST00000487519.6 NP_003192.1 Q00059-1E5KSU5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TFAMENST00000487519.6 linkc.221-680G>A intron_variant Intron 2 of 6 1 NM_003201.3 ENSP00000420588.1 Q00059-1
TFAMENST00000395377.2 linkc.164-680G>A intron_variant Intron 2 of 5 2 ENSP00000378776.2 H7BYN3
TFAMENST00000373895.7 linkc.221-680G>A intron_variant Intron 2 of 5 2 ENSP00000363002.3 Q00059-2
TFAMENST00000373899.3 linkn.491-680G>A intron_variant Intron 3 of 7 2

Frequencies

GnomAD3 genomes
AF:
0.526
AC:
79979
AN:
151968
Hom.:
22994
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.779
Gnomad AMI
AF:
0.564
Gnomad AMR
AF:
0.442
Gnomad ASJ
AF:
0.488
Gnomad EAS
AF:
0.488
Gnomad SAS
AF:
0.413
Gnomad FIN
AF:
0.345
Gnomad MID
AF:
0.440
Gnomad NFE
AF:
0.433
Gnomad OTH
AF:
0.518
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.526
AC:
80054
AN:
152086
Hom.:
23020
Cov.:
32
AF XY:
0.518
AC XY:
38505
AN XY:
74322
show subpopulations
African (AFR)
AF:
0.779
AC:
32306
AN:
41490
American (AMR)
AF:
0.442
AC:
6761
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.488
AC:
1695
AN:
3472
East Asian (EAS)
AF:
0.488
AC:
2525
AN:
5174
South Asian (SAS)
AF:
0.411
AC:
1982
AN:
4826
European-Finnish (FIN)
AF:
0.345
AC:
3641
AN:
10552
Middle Eastern (MID)
AF:
0.446
AC:
131
AN:
294
European-Non Finnish (NFE)
AF:
0.433
AC:
29415
AN:
67964
Other (OTH)
AF:
0.514
AC:
1085
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1759
3518
5277
7036
8795
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
686
1372
2058
2744
3430
<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:
0.480
Hom.:
6973
Bravo
AF:
0.546
Asia WGS
AF:
0.419
AC:
1458
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
5.0
DANN
Benign
0.58
PhyloP100
0.87
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs10826178; hg19: chr10-60147270; API