10-58386082-GTC-G

Position:

• chr10-58386082-GTC-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003201.3(TFAM):​c.102-134_102-133del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 771,028 control chromosomes in the GnomAD database, including 13,181 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3154 hom., cov: 28)
  • Exomes 𝑓: 0.18 (10027 hom.)
• Consequence: TFAM NM_003201.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.585

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-58386082-GTC-G is Benign according to our data. Variant chr10-58386082-GTC-G is described in ClinVar as [Benign]. Clinvar id is 1247413.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFAM	NM_003201.3	c.102-134_102-133del		intron_variant		ENST00000487519.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFAM	ENST00000487519.6	c.102-134_102-133del		intron_variant		1	NM_003201.3	P1
TFAM	ENST00000373895.7	c.102-134_102-133del		intron_variant		2
TFAM	ENST00000395377.2	c.46-134_46-133del		intron_variant		2
TFAM	ENST00000373899.3	n.305-134_305-133del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30136 AN: 152000 Hom.: 3154 Cov.: 28

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.177 AC: 109330 AN: 618910 Hom.: 10027 AF XY: 0.177 AC XY: 59434 AN XY: 336302

Gnomad4 AFR exome AF: 0.267

Gnomad4 AMR exome AF: 0.151

Gnomad4 ASJ exome AF: 0.204

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.198 AC: 30161 AN: 152118 Hom.: 3154 Cov.: 28 AF XY: 0.194 AC XY: 14439 AN XY: 74362

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.191

Alfa AF: 0.193 Hom.: 357

Bravo AF: 0.204

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs3830273; hg19: chr10-60145842;