19-7931102-TAAAAA-TAAAAAAA

Variant names:

• chr19-7931102-T-TAA
• rs58157552
• NM_006351.4:c.1038+34_1038+35dupTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_006351.4(TIMM44):​c.1038+34_1038+35dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00376 in 1,387,292 control chromosomes in the GnomAD database, including 6 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0056 (6 hom., cov: 30)
  • Exomes 𝑓: 0.0036 (0 hom.)
• Consequence: TIMM44 NM_006351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.175

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00563 (767/136242) while in subpopulation AFR AF= 0.0178 (659/37100). AF 95% confidence interval is 0.0166. There are 6 homozygotes in gnomad4. There are 373 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMM44	NM_006351.4	c.1038+34_1038+35dupTT		intron_variant	Intron 10 of 12	ENST00000270538.8	NP_006342.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TIMM44	ENST00000270538.8	c.1038+35_1038+36insTT		intron_variant	Intron 10 of 12	1	NM_006351.4	ENSP00000270538.2

Frequencies

GnomAD3 genomes AF: 0.00563 AC: 767 AN: 136206 Hom.: 6 Cov.: 30

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00569

Gnomad ASJ AF: 0.00245

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000127

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000144

Gnomad OTH AF: 0.00659

GnomAD4 exome AF: 0.00356 AC: 4450 AN: 1251050 Hom.: 0 Cov.: 0 AF XY: 0.00338 AC XY: 2119 AN XY: 626378

Gnomad4 AFR exome AF: 0.0205

Gnomad4 AMR exome AF: 0.00369

Gnomad4 ASJ exome AF: 0.00540

Gnomad4 EAS exome AF: 0.00121

Gnomad4 SAS exome AF: 0.00273

Gnomad4 FIN exome AF: 0.00334

Gnomad4 NFE exome AF: 0.00315

Gnomad4 OTH exome AF: 0.00382

GnomAD4 genome AF: 0.00563 AC: 767 AN: 136242 Hom.: 6 Cov.: 30 AF XY: 0.00568 AC XY: 373 AN XY: 65650

Gnomad4 AFR AF: 0.0178

Gnomad4 AMR AF: 0.00568

Gnomad4 ASJ AF: 0.00245

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000127

Gnomad4 NFE AF: 0.000144

Gnomad4 OTH AF: 0.00655

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58157552; hg19: chr19-7995987;