10-58385837-G-T

Variant names:

• chr10-58385837-G-T
• rs4397793
• NM_003201.3:c.101+189G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003201.3(TFAM):​c.101+189G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000921 in 152,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000092 (0 hom., cov: 32)
• Consequence: TFAM NM_003201.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 13 publications found

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 Gene-Disease associations (from GenCC):

• mitochondrial DNA depletion syndrome 15 (hepatocerebral type)

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003201.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAM	NM_003201.3	MANE Select	c.101+189G>T		intron	N/A	NP_003192.1	E5KSU5
	TFAM	NM_001270782.2		c.101+189G>T		intron	N/A	NP_001257711.1	Q00059-2
	TFAM	NR_073073.2		n.239+189G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAM	ENST00000487519.6	TSL:1 MANE Select	c.101+189G>T		intron	N/A	ENSP00000420588.1	Q00059-1
	TFAM	ENST00000909231.1		c.101+189G>T		intron	N/A	ENSP00000579290.1
	TFAM	ENST00000935269.1		c.101+189G>T		intron	N/A	ENSP00000605328.1

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 151928 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.000955

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

GnomAD4 genome AF: 0.0000921 AC: 14 AN: 152046 Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6 AN XY: 74334

African (AFR) AF: 0.00 AC: 0 AN: 41488

American (AMR) AF: 0.0000654 AC: 1 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67970

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.00 Hom.: 568

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.6
DANN	Benign	0.69
PhyloP100		-1.1
PromoterAI		-0.074	Neutral
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs4397793; hg19: chr10-60145597;