10-58395360-G-T

Position:

• chr10-58395360-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003201.3(TFAM):​c.*286G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 388,270 control chromosomes in the GnomAD database, including 6,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3156 hom., cov: 32)
  • Exomes 𝑓: 0.18 (3767 hom.)
• Consequence: TFAM NM_003201.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.463

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 10-58395360-G-T is Benign according to our data. Variant chr10-58395360-G-T is described in ClinVar as [Benign]. Clinvar id is 1245159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFAM	NM_003201.3	c.*286G>T		3_prime_UTR_variant	7/7	ENST00000487519.6	NP_003192.1
TFAM	NM_001270782.2	c.*286G>T		3_prime_UTR_variant	6/6		NP_001257711.1
TFAM	NR_073073.2	n.1232G>T		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFAM	ENST00000487519.6	c.*286G>T		3_prime_UTR_variant	7/7	1	NM_003201.3	ENSP00000420588.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30127 AN: 151798 Hom.: 3156 Cov.: 32

Gnomad AFR AF: 0.268

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: 0.104

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.176 AC: 41575 AN: 236354 Hom.: 3767 Cov.: 0 AF XY: 0.175 AC XY: 21920 AN XY: 125336

Gnomad4 AFR exome AF: 0.255

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.175

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.198 AC: 30148 AN: 151916 Hom.: 3156 Cov.: 32 AF XY: 0.194 AC XY: 14433 AN XY: 74268

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.189

Alfa AF: 0.176 Hom.: 3443

Bravo AF: 0.204

Asia WGS AF: 0.150 AC: 520 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.1
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1049432; hg19: chr10-60155120;