chr10-58387510-G-A

Variant names:

• chr10-58387510-G-A
• rs10826178
• NM_003201.3:c.221-680G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial DNA depletion syndrome 15 (hepatocerebral type)

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TFAM	NM_003201.3	c.221-680G>A		intron_variant	Intron 2 of 6	ENST00000487519.6	NP_003192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFAM	ENST00000487519.6	c.221-680G>A		intron_variant	Intron 2 of 6	1	NM_003201.3	ENSP00000420588.1
TFAM	ENST00000395377.2	c.164-680G>A		intron_variant	Intron 2 of 5	2		ENSP00000378776.2
TFAM	ENST00000373895.7	c.221-680G>A		intron_variant	Intron 2 of 5	2		ENSP00000363002.3
TFAM	ENST00000373899.3	n.491-680G>A		intron_variant	Intron 3 of 7	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

African (AFR) AF: 0.779 AC: 32306 AN: 41490

American (AMR) AF: 0.442 AC: 6761 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1695 AN: 3472

East Asian (EAS) AF: 0.488 AC: 2525 AN: 5174

South Asian (SAS) AF: 0.411 AC: 1982 AN: 4826

European-Finnish (FIN) AF: 0.345 AC: 3641 AN: 10552

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29415 AN: 67964

Other (OTH) AF: 0.514 AC: 1085 AN: 2110

Alfa AF: 0.480 Hom.: 6973

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
PhyloP100		0.87
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10826178; hg19: chr10-60147270;