10-58388016-A-G

Position:

• chr10-58388016-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003201.3(TFAM):​c.221-174A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 152,300 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.013 (12 hom., cov: 31)
• Consequence: TFAM NM_003201.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-58388016-A-G is Benign according to our data. Variant chr10-58388016-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1317894.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0127 (1930/152300) while in subpopulation AMR AF= 0.0247 (377/15284). AF 95% confidence interval is 0.0226. There are 12 homozygotes in gnomad4. There are 913 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFAM	NM_003201.3	c.221-174A>G		intron_variant		ENST00000487519.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFAM	ENST00000487519.6	c.221-174A>G		intron_variant		1	NM_003201.3	P1
TFAM	ENST00000373895.7	c.221-174A>G		intron_variant		2
TFAM	ENST00000395377.2	c.165-174A>G		intron_variant		2
TFAM	ENST00000373899.3	n.491-174A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1928 AN: 152182 Hom.: 12 Cov.: 31

Gnomad AFR AF: 0.00340

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00452

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0183

Gnomad OTH AF: 0.0148

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

GnomAD4 genome AF: 0.0127 AC: 1930 AN: 152300 Hom.: 12 Cov.: 31 AF XY: 0.0123 AC XY: 913 AN XY: 74476

Gnomad4 AFR AF: 0.00339

Gnomad4 AMR AF: 0.0247

Gnomad4 ASJ AF: 0.0176

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00452

Gnomad4 NFE AF: 0.0183

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0124 Hom.: 4

Bravo AF: 0.0134

Asia WGS AF: 0.00202 AC: 7 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

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.63

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: rs139675989; hg19: chr10-60147776;