rs1049432

Variant names:

• chr10-58395360-G-T
• rs1049432
• NM_003201.3:c.*286G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-58395360-G-T
• chr10-58395360-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003201.3(TFAM):​c.*286G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 388,270 control chromosomes in the GnomAD database, including 6,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3156 hom., cov: 32)
  • Exomes 𝑓: 0.18 (3767 hom.)
• Consequence: TFAM NM_003201.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.463
• Publications: 28 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: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 10-58395360-G-T is Benign according to our data. Variant chr10-58395360-G-T is described in ClinVar as Benign. ClinVar VariationId is 1245159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

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.*286G>T		3_prime_UTR	Exon 7 of 7	NP_003192.1	E5KSU5
	TFAM	NM_001270782.2		c.*286G>T		3_prime_UTR	Exon 6 of 6	NP_001257711.1	Q00059-2
	TFAM	NR_073073.2		n.1232G>T		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAM	ENST00000487519.6	TSL:1 MANE Select	c.*286G>T		3_prime_UTR	Exon 7 of 7	ENSP00000420588.1	Q00059-1
	TFAM	ENST00000909231.1		c.*286G>T		3_prime_UTR	Exon 7 of 7	ENSP00000579290.1
	TFAM	ENST00000935269.1		c.*286G>T		3_prime_UTR	Exon 7 of 7	ENSP00000605328.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30127 AN: 151798 Hom.: 3156 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.176 AC: 41575 AN: 236354 Hom.: 3767 Cov.: 0 AF XY: 0.175 AC XY: 21920 AN XY: 125336

African (AFR) AF: 0.255 AC: 1934 AN: 7580

American (AMR) AF: 0.152 AC: 1297 AN: 8530

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 1433 AN: 7566

East Asian (EAS) AF: 0.175 AC: 2373 AN: 13546

South Asian (SAS) AF: 0.169 AC: 5380 AN: 31848

European-Finnish (FIN) AF: 0.103 AC: 990 AN: 9566

Middle Eastern (MID) AF: 0.171 AC: 175 AN: 1024

European-Non Finnish (NFE) AF: 0.179 AC: 25554 AN: 142956

Other (OTH) AF: 0.178 AC: 2439 AN: 13738

GnomAD4 genome AF: 0.198 AC: 30148 AN: 151916 Hom.: 3156 Cov.: 32 AF XY: 0.194 AC XY: 14433 AN XY: 74268

African (AFR) AF: 0.268 AC: 11085 AN: 41400

American (AMR) AF: 0.163 AC: 2485 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 690 AN: 3468

East Asian (EAS) AF: 0.172 AC: 886 AN: 5164

South Asian (SAS) AF: 0.170 AC: 821 AN: 4816

European-Finnish (FIN) AF: 0.104 AC: 1096 AN: 10572

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12400 AN: 67928

Other (OTH) AF: 0.189 AC: 399 AN: 2106

Alfa AF: 0.185 Hom.: 8382

Bravo AF: 0.204

Asia WGS AF: 0.150 AC: 520 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.1
DANN	Benign	0.63
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1049432; hg19: chr10-60155120;