rs11006132

Variant names:

• chr10-58396406-A-G
• rs11006132
• NM_003201.3:c.*1332A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003201.3(TFAM):​c.*1332A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,174 control chromosomes in the GnomAD database, including 4,470 homozygotes. 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 0.24 (4470 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TFAM NM_003201.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.611
• Publications: 22 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFAM	NM_003201.3	c.*1332A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000487519.6	NP_003192.1
TFAM	NR_073073.2	n.2278A>G		non_coding_transcript_exon_variant	Exon 8 of 8
TFAM	NM_001270782.2	c.*1332A>G		3_prime_UTR_variant	Exon 6 of 6		NP_001257711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFAM	ENST00000487519.6	c.*1332A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_003201.3	ENSP00000420588.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36126 AN: 152054 Hom.: 4471 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.243

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.238 AC: 36142 AN: 152174 Hom.: 4470 Cov.: 33 AF XY: 0.232 AC XY: 17276 AN XY: 74388

African (AFR) AF: 0.280 AC: 11639 AN: 41516

American (AMR) AF: 0.208 AC: 3180 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1190 AN: 3472

East Asian (EAS) AF: 0.174 AC: 902 AN: 5182

South Asian (SAS) AF: 0.194 AC: 935 AN: 4830

European-Finnish (FIN) AF: 0.128 AC: 1351 AN: 10584

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16072 AN: 67986

Other (OTH) AF: 0.241 AC: 508 AN: 2112

Alfa AF: 0.239 Hom.: 6737

Bravo AF: 0.245

Asia WGS AF: 0.166 AC: 577 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.5
DANN	Benign	0.78
PhyloP100		-0.61
Mutation Taster		=100/0	polymorphism (auto)

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: rs11006132; hg19: chr10-60156166;