19-7931102-TAAAAA-TAAAA

Variant names:

• chr19-7931102-TA-T
• rs58157552
• NM_006351.4:c.1038+35delT

Variant summary

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

The NM_006351.4(TIMM44):​c.1038+35delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,237,228 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 30)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: TIMM44 NM_006351.4 intron
• Clinical Significance: Likely 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-TA-T is Benign according to our data. Variant chr19-7931102-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1317407.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TIMM44	NM_006351.4	c.1038+35delT		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+35delT		intron_variant	Intron 10 of 12	1	NM_006351.4	ENSP00000270538.2

Frequencies

GnomAD3 genomes AF: 0.00221 AC: 300 AN: 135812 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000784

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00300

Gnomad ASJ AF: 0.00276

Gnomad EAS AF: 0.00128

Gnomad SAS AF: 0.000235

Gnomad FIN AF: 0.00952

Gnomad MID AF: 0.00338

Gnomad NFE AF: 0.00211

Gnomad OTH AF: 0.00441

GnomAD4 exome AF: 0.112 AC: 123699 AN: 1101380 Hom.: 0 Cov.: 0 AF XY: 0.112 AC XY: 61344 AN XY: 548252

Gnomad4 AFR exome AF: 0.0841

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.111

Gnomad4 OTH exome AF: 0.115

GnomAD4 genome AF: 0.00222 AC: 302 AN: 135848 Hom.: 0 Cov.: 30 AF XY: 0.00245 AC XY: 160 AN XY: 65396

Gnomad4 AFR AF: 0.000863

Gnomad4 AMR AF: 0.00300

Gnomad4 ASJ AF: 0.00276

Gnomad4 EAS AF: 0.00107

Gnomad4 SAS AF: 0.000236

Gnomad4 FIN AF: 0.00952

Gnomad4 NFE AF: 0.00211

Gnomad4 OTH AF: 0.00438

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jan 27, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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;