10-58385498-A-G

Position:

• chr10-58385498-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.-50A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,423,766 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0039 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (28 hom.)
• Consequence: TFAM NM_003201.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.03

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=-0.99).
• BP6: Variant 10-58385498-A-G is Benign according to our data. Variant chr10-58385498-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1318234.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFAM	NM_003201.3	c.-50A>G		5_prime_UTR_variant	1/7	ENST00000487519.6	NP_003192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFAM	ENST00000487519	c.-50A>G		5_prime_UTR_variant	1/7	1	NM_003201.3	ENSP00000420588.1
TFAM	ENST00000373895	c.-50A>G		5_prime_UTR_variant	1/6	2		ENSP00000363002.3
TFAM	ENST00000373899.3	n.154A>G		non_coding_transcript_exon_variant	1/8	2

Frequencies

GnomAD3 genomes AF: 0.00393 AC: 598 AN: 152080 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00113

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0166

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00434

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00395 AC: 617 AN: 156380 Hom.: 7 AF XY: 0.00371 AC XY: 305 AN XY: 82302

Gnomad AFR exome AF: 0.000912

Gnomad AMR exome AF: 0.00339

Gnomad ASJ exome AF: 0.000117

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000263

Gnomad FIN exome AF: 0.0172

Gnomad NFE exome AF: 0.00410

Gnomad OTH exome AF: 0.00272

GnomAD4 exome AF: 0.00466 AC: 5930 AN: 1271570 Hom.: 28 Cov.: 19 AF XY: 0.00452 AC XY: 2864 AN XY: 633542

Gnomad4 AFR exome AF: 0.000754

Gnomad4 AMR exome AF: 0.00374

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000284

Gnomad4 SAS exome AF: 0.000442

Gnomad4 FIN exome AF: 0.0158

Gnomad4 NFE exome AF: 0.00497

Gnomad4 OTH exome AF: 0.00336

GnomAD4 genome AF: 0.00393 AC: 598 AN: 152196 Hom.: 5 Cov.: 32 AF XY: 0.00406 AC XY: 302 AN XY: 74408

Gnomad4 AFR AF: 0.00113

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0166

Gnomad4 NFE AF: 0.00434

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00251 Hom.: 1

Bravo AF: 0.00280

Asia WGS AF: 0.000289 AC: 1 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 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.3
DANN	Benign	0.32

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: rs41283686; hg19: chr10-60145258;