Variant 10-58388174-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003201.3(TFAM):c.221-16T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0329 in 1,610,580 control chromosomes in the GnomAD database, including 1,148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 83 hom., cov: 33)

Exomes 𝑓: 0.033 ( 1065 hom. )

Consequence

TFAM
NM_003201.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.522

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 10-58388174-T-C is Benign according to our data. Variant chr10-58388174-T-C is described in ClinVar as [Benign]. Clinvar id is 672912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFAM	NM_003201.3 linkuse as main transcript	c.221-16T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000487519.6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
TFAM	ENST00000487519.6 linkuse as main transcript	c.221-16T>C	splice_polypyrimidine_tract_variant, intron_variant	1	NM_003201.3	P1	Q00059-1
TFAM	ENST00000373895.7 linkuse as main transcript	c.221-16T>C	splice_polypyrimidine_tract_variant, intron_variant	2			Q00059-2
TFAM	ENST00000395377.2 linkuse as main transcript	c.165-16T>C	splice_polypyrimidine_tract_variant, intron_variant	2
TFAM	ENST00000373899.3 linkuse as main transcript	n.491-16T>C	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0277

AC:

4208

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00574

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.0498

Gnomad SAS

AF:

0.0729

Gnomad FIN

AF:

0.0761

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0329

Gnomad OTH

AF:

0.0321

GnomAD3 exomes

AF:

0.0364

AC:

9113

AN:

250308

Hom.:

244

AF XY:

0.0393

AC XY:

5328

AN XY:

135584

show subpopulations

Gnomad AFR exome

AF:

0.00611

Gnomad AMR exome

AF:

0.0109

Gnomad ASJ exome

AF:

0.0111

Gnomad EAS exome

AF:

0.0524

Gnomad SAS exome

AF:

0.0731

Gnomad FIN exome

AF:

0.0727

Gnomad NFE exome

AF:

0.0315

Gnomad OTH exome

AF:

0.0330

GnomAD4 exome

AF:

0.0334

AC:

48764

AN:

1458282

Hom.:

1065

Cov.:

AF XY:

0.0348

AC XY:

25274

AN XY:

725724

show subpopulations

Gnomad4 AFR exome

AF:

0.00389

Gnomad4 AMR exome

AF:

0.0119

Gnomad4 ASJ exome

AF:

0.0120

Gnomad4 EAS exome

AF:

0.0541

Gnomad4 SAS exome

AF:

0.0732

Gnomad4 FIN exome

AF:

0.0699

Gnomad4 NFE exome

AF:

0.0302

Gnomad4 OTH exome

AF:

0.0325

GnomAD4 genome

AF:

0.0276

AC:

4202

AN:

152298

Hom.:

Cov.:

AF XY:

0.0304

AC XY:

2261

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00573

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.0490

Gnomad4 SAS

AF:

0.0736

Gnomad4 FIN

AF:

0.0761

Gnomad4 NFE

AF:

0.0329

Gnomad4 OTH

AF:

0.0318

Alfa

AF:

0.0294

Hom.:

Bravo

AF:

0.0210

Asia WGS

AF:

0.0870

AC:

302

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 22, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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