10-58386014-A-G

Position:

• chr10-58386014-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_003201.3(TFAM):​c.102-206A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0082 in 152,108 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.0082 (13 hom., cov: 33)
• Consequence: TFAM NM_003201.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.182

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-58386014-A-G is Benign according to our data. Variant chr10-58386014-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1318157.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFAM	NM_003201.3	c.102-206A>G		intron_variant		ENST00000487519.6	NP_003192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFAM	ENST00000487519.6	c.102-206A>G		intron_variant		1	NM_003201.3	ENSP00000420588.1
TFAM	ENST00000395377.2	c.45-206A>G		intron_variant		2		ENSP00000378776.2
TFAM	ENST00000373895.7	c.102-206A>G		intron_variant		2		ENSP00000363002.3
TFAM	ENST00000373899.3	n.305-206A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00821 AC: 1248 AN: 151990 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00952

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.00239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00820 AC: 1247 AN: 152108 Hom.: 13 Cov.: 33 AF XY: 0.00756 AC XY: 562 AN XY: 74360

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00359

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00952

Gnomad4 NFE AF: 0.0150

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.0160 Hom.: 4

Bravo AF: 0.00646

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.75

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: rs72797429; hg19: chr10-60145774;