19-7927167-A-C

Variant names:

• chr19-7927167-A-C
• rs12976850
• NM_006351.4:c.*20T>G

Variant summary

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

The NM_006351.4(TIMM44):​c.*20T>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 0.0702 in 1,600,524 control chromosomes in the GnomAD database, including 4,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.077 (462 hom., cov: 33)
  • Exomes 𝑓: 0.070 (3604 hom.)
• Consequence: TIMM44 NM_006351.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.864

Genes affected

TIMM44 (HGNC:17316): (translocase of inner mitochondrial membrane 44) This gene encodes a peripheral membrane protein associated with the mitochondrial inner membrane translocase, which functions in the import of proteins across the mitochondrial inner membrane and into the mitochondrial matrix. The encoded protein mediates binding of mitochondrial heat shock protein 70 to the translocase of inner mitochondrial membrane 23 (TIM23) complex. Expression of this gene is upregulated in kidney in a mouse model of diabetes. A mutation in this gene is associated with familial oncocytic thyroid carcinoma. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-7927167-A-C is Benign according to our data. Variant chr19-7927167-A-C is described in ClinVar as [Benign]. Clinvar id is 137650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMM44	NM_006351.4	c.*20T>G		3_prime_UTR_variant	Exon 13 of 13	ENST00000270538.8	NP_006342.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMM44	ENST00000270538	c.*20T>G		3_prime_UTR_variant	Exon 13 of 13	1	NM_006351.4	ENSP00000270538.2

Frequencies

GnomAD3 genomes AF: 0.0765 AC: 11643 AN: 152138 Hom.: 461 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0584

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.0432

Gnomad SAS AF: 0.0482

Gnomad FIN AF: 0.0664

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0716

Gnomad OTH AF: 0.0756

GnomAD3 exomes AF: 0.0610 AC: 14070 AN: 230638 Hom.: 426 AF XY: 0.0608 AC XY: 7690 AN XY: 126464

Gnomad AFR exome AF: 0.100

Gnomad AMR exome AF: 0.0361

Gnomad ASJ exome AF: 0.0710

Gnomad EAS exome AF: 0.0362

Gnomad SAS exome AF: 0.0539

Gnomad FIN exome AF: 0.0695

Gnomad NFE exome AF: 0.0674

Gnomad OTH exome AF: 0.0609

GnomAD4 exome AF: 0.0695 AC: 100680 AN: 1448268 Hom.: 3604 Cov.: 32 AF XY: 0.0690 AC XY: 49691 AN XY: 720612

Gnomad4 AFR exome AF: 0.0997

Gnomad4 AMR exome AF: 0.0376

Gnomad4 ASJ exome AF: 0.0706

Gnomad4 EAS exome AF: 0.0485

Gnomad4 SAS exome AF: 0.0565

Gnomad4 FIN exome AF: 0.0698

Gnomad4 NFE exome AF: 0.0716

Gnomad4 OTH exome AF: 0.0691

GnomAD4 genome AF: 0.0765 AC: 11652 AN: 152256 Hom.: 462 Cov.: 33 AF XY: 0.0756 AC XY: 5631 AN XY: 74440

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0584

Gnomad4 ASJ AF: 0.0732

Gnomad4 EAS AF: 0.0433

Gnomad4 SAS AF: 0.0481

Gnomad4 FIN AF: 0.0664

Gnomad4 NFE AF: 0.0716

Gnomad4 OTH AF: 0.0748

Alfa AF: 0.0727 Hom.: 133

Bravo AF: 0.0742

Asia WGS AF: 0.0490 AC: 171 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Jan 09, 2014

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.67

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: rs12976850; hg19: chr19-7992052;