Variant 10-58385498-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003201.3(TFAM):c.-50A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,423,766 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0039 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 28 hom. )

Consequence

TFAM
NM_003201.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.03

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 10-58385498-A-G is Benign according to our data. Variant chr10-58385498-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1318234.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFAM	NM_003201.3 linkuse as main transcript	c.-50A>G		5_prime_UTR_variant	1/7	ENST00000487519.6

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFAM	ENST00000487519.6 linkuse as main transcript	c.-50A>G	5_prime_UTR_variant	1/7	1	NM_003201.3	P1	Q00059-1
TFAM	ENST00000373895.7 linkuse as main transcript	c.-50A>G	5_prime_UTR_variant	1/6	2			Q00059-2
TFAM	ENST00000373899.3 linkuse as main transcript	n.154A>G	non_coding_transcript_exon_variant	1/8	2

Frequencies

GnomAD3 genomes

AF:

0.00393

AC:

598

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00113

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0166

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00434

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00395

AC:

617

AN:

156380

Hom.:

AF XY:

0.00371

AC XY:

305

AN XY:

82302

show subpopulations

Gnomad AFR exome

AF:

0.000912

Gnomad AMR exome

AF:

0.00339

Gnomad ASJ exome

AF:

0.000117

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000263

Gnomad FIN exome

AF:

0.0172

Gnomad NFE exome

AF:

0.00410

Gnomad OTH exome

AF:

0.00272

GnomAD4 exome

AF:

0.00466

AC:

5930

AN:

1271570

Hom.:

Cov.:

AF XY:

0.00452

AC XY:

2864

AN XY:

633542

show subpopulations

Gnomad4 AFR exome

AF:

0.000754

Gnomad4 AMR exome

AF:

0.00374

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000284

Gnomad4 SAS exome

AF:

0.000442

Gnomad4 FIN exome

AF:

0.0158

Gnomad4 NFE exome

AF:

0.00497

Gnomad4 OTH exome

AF:

0.00336

GnomAD4 genome

AF:

0.00393

AC:

598

AN:

152196

Hom.:

Cov.:

AF XY:

0.00406

AC XY:

302

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0166

Gnomad4 NFE

AF:

0.00434

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00251

Hom.:

Bravo

AF:

0.00280

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

2.3

DANN

Benign

0.32

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