14-58427073-T-G

Position:

• chr14-58427073-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012460.4(TIMM9):​c.-134A>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 154,172 control chromosomes in the GnomAD database, including 55,196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (54366 hom., cov: 33)
  • Exomes 𝑓: 0.91 (830 hom.)
• Consequence: TIMM9 NM_012460.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0660

Genes affected

TIMM9 (HGNC:11819): (translocase of inner mitochondrial membrane 9) TIMM9 belongs to a family of evolutionarily conserved proteins that are organized in heterooligomeric complexes in the mitochondrial intermembrane space. These proteins mediate the import and insertion of hydrophobic membrane proteins into the mitochondrial inner membrane.[supplied by OMIM, Apr 2004]

TIMM9 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 14-58427073-T-G is Benign according to our data. Variant chr14-58427073-T-G is described in ClinVar as [Benign]. Clinvar id is 1279463.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMM9	NM_012460.4	c.-134A>C		5_prime_UTR_premature_start_codon_gain_variant	2/6	ENST00000395159.7	NP_036592.1
TIMM9	NM_012460.4	c.-134A>C		5_prime_UTR_variant	2/6	ENST00000395159.7	NP_036592.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMM9	ENST00000395159.7	c.-134A>C		5_prime_UTR_premature_start_codon_gain_variant	2/6	1	NM_012460.4	ENSP00000378588.2
TIMM9	ENST00000395159.7	c.-134A>C		5_prime_UTR_variant	2/6	1	NM_012460.4	ENSP00000378588.2

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126203 AN: 152078 Hom.: 54370 Cov.: 33

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.921

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.950

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.928

Gnomad OTH AF: 0.853

GnomAD4 exome AF: 0.912 AC: 1803 AN: 1976 Hom.: 830 Cov.: 0 AF XY: 0.905 AC XY: 1119 AN XY: 1236

Gnomad4 AFR exome AF: 0.417

Gnomad4 AMR exome AF: 0.934

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.870

Gnomad4 FIN exome AF: 0.943

Gnomad4 NFE exome AF: 0.925

Gnomad4 OTH exome AF: 0.962

GnomAD4 genome AF: 0.829 AC: 126223 AN: 152196 Hom.: 54366 Cov.: 33 AF XY: 0.833 AC XY: 61960 AN XY: 74410

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.915

Gnomad4 ASJ AF: 0.921

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.876

Gnomad4 FIN AF: 0.950

Gnomad4 NFE AF: 0.928

Gnomad4 OTH AF: 0.853

Alfa AF: 0.859 Hom.: 13868

Bravo AF: 0.818

Asia WGS AF: 0.903 AC: 3141 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.6
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6764; hg19: chr14-58893791;