rs3900887

Positions:

• chr10-58386035-T-A

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.102-185T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,170 control chromosomes in the GnomAD database, including 1,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.15 (1728 hom., cov: 32)
• Consequence: TFAM NM_003201.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.659

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 10-58386035-T-A is Benign according to our data. Variant chr10-58386035-T-A is described in ClinVar as [Benign]. Clinvar id is 1243323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFAM	NM_003201.3	c.102-185T>A		intron_variant		ENST00000487519.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFAM	ENST00000487519.6	c.102-185T>A		intron_variant		1	NM_003201.3	P1
TFAM	ENST00000373895.7	c.102-185T>A		intron_variant		2
TFAM	ENST00000395377.2	c.46-185T>A		intron_variant		2
TFAM	ENST00000373899.3	n.305-185T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22956 AN: 152052 Hom.: 1730 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0745

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.151 AC: 22959 AN: 152170 Hom.: 1728 Cov.: 32 AF XY: 0.148 AC XY: 10979 AN XY: 74404

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0741

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.153

Alfa AF: 0.153 Hom.: 217

Bravo AF: 0.149

Asia WGS AF: 0.0380 AC: 132 AN: 3478

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	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.3
DANN	Benign	0.85

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: rs3900887; hg19: chr10-60145795;