10-58385837-G-C

Position:

• chr10-58385837-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003201.3(TFAM):​c.101+189G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,984 control chromosomes in the GnomAD database, including 19,577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (19577 hom., cov: 32)
• Consequence: TFAM NM_003201.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06

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=-0.88).
• BP6: Variant 10-58385837-G-C is Benign according to our data. Variant chr10-58385837-G-C is described in ClinVar as [Benign]. Clinvar id is 684179.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TFAM	NM_003201.3	c.101+189G>C		intron_variant		ENST00000487519.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TFAM	ENST00000487519.6	c.101+189G>C		intron_variant		1	NM_003201.3	P1
TFAM	ENST00000373895.7	c.101+189G>C		intron_variant		2
TFAM	ENST00000395377.2	c.45+189G>C		intron_variant		2
TFAM	ENST00000373899.3	n.304+189G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74351 AN: 151868 Hom.: 19560 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.490 AC: 74417 AN: 151984 Hom.: 19577 Cov.: 32 AF XY: 0.483 AC XY: 35852 AN XY: 74300

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.415

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.475

Alfa AF: 0.268 Hom.: 568

Bravo AF: 0.507

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.73

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: rs4397793; hg19: chr10-60145597; COSMIC: COSV65876682;