19-7931102-T-TA

Position:

• chr19-7931102-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_006351.4(TIMM44):​c.1038+35_1038+36insT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 135,820 control chromosomes in the GnomAD database, including 936 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (936 hom., cov: 30)
  • Exomes 𝑓: 0.24 (184 hom.)
  • Failed GnomAD Quality Control
• Consequence: TIMM44 NM_006351.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 19-7931102-T-TA is Benign according to our data. Variant chr19-7931102-T-TA is described in ClinVar as [Benign]. Clinvar id is 1291438.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TIMM44	NM_006351.4	c.1038+35_1038+36insT		intron_variant		ENST00000270538.8	NP_006342.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TIMM44	ENST00000270538.8	c.1038+35_1038+36insT		intron_variant		1	NM_006351.4	ENSP00000270538	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 15327 AN: 135788 Hom.: 932 Cov.: 30

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0940

Gnomad AMR AF: 0.0849

Gnomad ASJ AF: 0.0843

Gnomad EAS AF: 0.0451

Gnomad SAS AF: 0.0551

Gnomad FIN AF: 0.0863

Gnomad MID AF: 0.0777

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.122

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.242 AC: 261280 AN: 1078312 Hom.: 184 Cov.: 0 AF XY: 0.241 AC XY: 129328 AN XY: 536670

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.195

Gnomad4 ASJ exome AF: 0.243

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.236

Gnomad4 NFE exome AF: 0.246

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.113 AC: 15348 AN: 135820 Hom.: 936 Cov.: 30 AF XY: 0.113 AC XY: 7401 AN XY: 65408

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0848

Gnomad4 ASJ AF: 0.0843

Gnomad4 EAS AF: 0.0453

Gnomad4 SAS AF: 0.0549

Gnomad4 FIN AF: 0.0863

Gnomad4 NFE AF: 0.0852

Gnomad4 OTH AF: 0.122

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs58157552; hg19: chr19-7995987;