14-58427095-G-C

Position:

• chr14-58427095-G-C

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.-156C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 158,722 control chromosomes in the GnomAD database, including 57,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.83 (54335 hom., cov: 33)
  • Exomes 𝑓: 0.91 (2692 hom.)
• Consequence: TIMM9 NM_012460.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.03

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=-0.88).
• BP6: Variant 14-58427095-G-C is Benign according to our data. Variant chr14-58427095-G-C is described in ClinVar as [Benign]. Clinvar id is 1283831.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.-156C>G		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.-156C>G		5_prime_UTR_variant	2/6	1	NM_012460.4	ENSP00000378588.2

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126154 AN: 152084 Hom.: 54339 Cov.: 33

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.914

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: 0.852

GnomAD4 exome AF: 0.905 AC: 5902 AN: 6520 Hom.: 2692 Cov.: 0 AF XY: 0.899 AC XY: 3490 AN XY: 3880

Gnomad4 AFR exome AF: 0.536

Gnomad4 AMR exome AF: 0.928

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.990

Gnomad4 SAS exome AF: 0.852

Gnomad4 FIN exome AF: 0.944

Gnomad4 NFE exome AF: 0.918

Gnomad4 OTH exome AF: 0.921

GnomAD4 genome AF: 0.829 AC: 126174 AN: 152202 Hom.: 54335 Cov.: 33 AF XY: 0.832 AC XY: 61936 AN XY: 74424

Gnomad4 AFR AF: 0.568

Gnomad4 AMR AF: 0.914

Gnomad4 ASJ AF: 0.921

Gnomad4 EAS AF: 0.987

Gnomad4 SAS AF: 0.875

Gnomad4 FIN AF: 0.950

Gnomad4 NFE AF: 0.928

Gnomad4 OTH AF: 0.853

Alfa AF: 0.869 Hom.: 7293

Bravo AF: 0.818

Asia WGS AF: 0.903 AC: 3140 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	-0.88
CADD	Benign	7.4
DANN	Benign	0.69
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: rs6763; hg19: chr14-58893813;