rs10826178

chr10-58387510-G-Achr10-58387510-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.869

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 -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/exons	MANE	UniProt
TFAM	NM_003201.3	c.221-680G>A		intron_variant		ENST00000487519.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFAM	ENST00000487519.6	c.221-680G>A		intron_variant		1	NM_003201.3	P1
TFAM	ENST00000373895.7	c.221-680G>A		intron_variant		2
TFAM	ENST00000395377.2	c.165-680G>A		intron_variant		2
TFAM	ENST00000373899.3	n.491-680G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.526 AC: 79979 AN: 151968 Hom.: 22994 Cov.: 32

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

Gnomad4 AFR AF: 0.779

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.514

Alfa AF: 0.468 Hom.: 3602

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

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: rs10826178; hg19: chr10-60147270;