19-7931102-TAAAAAA-T

Variant names:

• chr19-7931102-TAAAAAA-T
• rs58157552
• NM_006351.4:c.1038+30_1038+35delTTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006351.4(TIMM44):​c.1038+30_1038+35delTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000791 in 1,263,850 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: TIMM44 NM_006351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475
• Publications: 0 publications found

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]

TIMM44 Gene-Disease associations (from GenCC):

• thyroid cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006351.4. 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
	TIMM44	NM_006351.4	MANE Select	c.1038+30_1038+35delTTTTTT		intron	N/A	NP_006342.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TIMM44	ENST00000270538.8	TSL:1 MANE Select	c.1038+30_1038+35delTTTTTT		intron	N/A	ENSP00000270538.2	O43615
	TIMM44	ENST00000595876.5	TSL:1	n.*726+30_*726+35delTTTTTT		intron	N/A	ENSP00000471596.1	M0R124
	TIMM44	ENST00000923643.1		c.1026+30_1026+35delTTTTTT		intron	N/A	ENSP00000593702.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.91e-7 AC: 1 AN: 1263850 Hom.: 0 AF XY: 0.00000158 AC XY: 1 AN XY: 632674

African (AFR) AF: 0.00 AC: 0 AN: 28992

American (AMR) AF: 0.00 AC: 0 AN: 38506

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23624

East Asian (EAS) AF: 0.00 AC: 0 AN: 35780

South Asian (SAS) AF: 0.0000128 AC: 1 AN: 78354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48046

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5244

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 952452

Other (OTH) AF: 0.00 AC: 0 AN: 52852

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs58157552; hg19: chr19-7995987;