Variant 10-58386301-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003201.3(TFAM):c.183T>C(p.Ser61=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0186 in 1,613,840 control chromosomes in the GnomAD database, including 321 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 23 hom., cov: 32)

Exomes 𝑓: 0.019 ( 298 hom. )

Consequence

TFAM
NM_003201.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.784

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 10-58386301-T-C is Benign according to our data. Variant chr10-58386301-T-C is described in ClinVar as [Benign]. Clinvar id is 669577.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.784 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0153 (2325/152322) while in subpopulation NFE AF= 0.0215 (1460/68018). AF 95% confidence interval is 0.0205. There are 23 homozygotes in gnomad4. There are 1130 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFAM	NM_003201.3 linkuse as main transcript	c.183T>C	p.Ser61=	synonymous_variant	2/7	ENST00000487519.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFAM	ENST00000487519.6 linkuse as main transcript	c.183T>C	p.Ser61=	synonymous_variant	2/7	1	NM_003201.3	P1	Q00059-1
TFAM	ENST00000395377.2 linkuse as main transcript	c.129T>C	p.Ser43=	synonymous_variant	2/6	2
TFAM	ENST00000373895.7 linkuse as main transcript	c.183T>C	p.Ser61=	synonymous_variant	2/6	2			Q00059-2
TFAM	ENST00000373899.3 linkuse as main transcript	n.386T>C		non_coding_transcript_exon_variant	2/8	2

Frequencies

GnomAD3 genomes

AF:

0.0153

AC:

2327

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00335

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0199

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.0230

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0215

Gnomad OTH

AF:

0.0230

GnomAD3 exomes

AF:

0.0168

AC:

4229

AN:

251426

Hom.:

AF XY:

0.0176

AC XY:

2393

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00265

Gnomad AMR exome

AF:

0.0129

Gnomad ASJ exome

AF:

0.0222

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0104

Gnomad FIN exome

AF:

0.0241

Gnomad NFE exome

AF:

0.0222

Gnomad OTH exome

AF:

0.0235

GnomAD4 exome

AF:

0.0189

AC:

27654

AN:

1461518

Hom.:

298

Cov.:

AF XY:

0.0189

AC XY:

13735

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.00269

Gnomad4 AMR exome

AF:

0.0138

Gnomad4 ASJ exome

AF:

0.0188

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0105

Gnomad4 FIN exome

AF:

0.0253

Gnomad4 NFE exome

AF:

0.0206

Gnomad4 OTH exome

AF:

0.0182

GnomAD4 genome

AF:

0.0153

AC:

2325

AN:

152322

Hom.:

Cov.:

AF XY:

0.0152

AC XY:

1130

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00332

Gnomad4 AMR

AF:

0.0199

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0106

Gnomad4 FIN

AF:

0.0230

Gnomad4 NFE

AF:

0.0215

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0184

Hom.:

Bravo

AF:

0.0146

Asia WGS

AF:

0.00549

AC:

AN:

3478

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 26, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 24, 2019	This variant is associated with the following publications: (PMID: 20863902, 18248889) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

7.0

DANN

Benign

0.69

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