chr17-16029111-T-C

Variant names:

• chr17-16029111-T-C
• rs117133932
• NM_017775.4:c.*1589T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_017775.4(TTC19):​c.*1589T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0326 in 445,342 control chromosomes in the GnomAD database, including 311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (91 hom., cov: 31)
  • Exomes 𝑓: 0.034 (220 hom.)
• Consequence: TTC19 NM_017775.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.913

Genes affected

TTC19 (HGNC:26006): (tetratricopeptide repeat domain 19) This gene encodes a protein with a tetratricopeptide repeat (TPR) domain containing several TPRs of about 34 aa each. These repeats are found in a variety of organisms including bacteria, fungi and plants, and are involved in a variety of functions including protein-protein interactions. This protein is embedded in the inner mitochondrial membrane and is involved in the formation of the mitochondrial respiratory chain III. It has also been suggested that this protein plays a role in cytokinesis. Mutations in this gene cause mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2012]

NCOR1 (HGNC:7672): (nuclear receptor corepressor 1) This gene encodes a protein that mediates ligand-independent transcription repression of thyroid-hormone and retinoic-acid receptors by promoting chromatin condensation and preventing access of the transcription machinery. It is part of a complex which also includes histone deacetylases and transcriptional regulators similar to the yeast protein Sin3p. This gene is located between the Charcot-Marie-Tooth and Smith-Magenis syndrome critical regions on chromosome 17. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 17 and 20.[provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 17-16029111-T-C is Benign according to our data. Variant chr17-16029111-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 891562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0291 (4352/149690) while in subpopulation NFE AF = 0.0435 (2901/66644). AF 95% confidence interval is 0.0422. There are 91 homozygotes in GnomAd4. There are 2103 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position FAILED quality control check.
• BS2: High Homozygotes in GnomAd4 at 91 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC19	NM_017775.4	c.*1589T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000261647.10	NP_060245.3
NCOR1	NM_006311.4	c.*3185A>G		downstream_gene_variant		ENST00000268712.8	NP_006302.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC19	ENST00000261647.10	c.*1589T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_017775.4	ENSP00000261647.5
NCOR1	ENST00000268712.8	c.*3185A>G		downstream_gene_variant		1	NM_006311.4	ENSP00000268712.2

Frequencies

GnomAD3 genomes AF: 0.0291 AC: 4354 AN: 149568 Hom.: 91 Cov.: 31

Gnomad AFR AF: 0.00843

Gnomad AMI AF: 0.00118

Gnomad AMR AF: 0.0207

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.0510

Gnomad MID AF: 0.0227

Gnomad NFE AF: 0.0435

Gnomad OTH AF: 0.0290

GnomAD2 exomes AF: 0.0290 AC: 3578 AN: 123262 AF XY: 0.0297

Gnomad AFR exome AF: 0.00712

Gnomad AMR exome AF: 0.0142

Gnomad ASJ exome AF: 0.0386

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0544

Gnomad NFE exome AF: 0.0460

Gnomad OTH exome AF: 0.0311

GnomAD4 exome AF: 0.0343 AC: 10150 AN: 295652 Hom.: 220 Cov.: 0 AF XY: 0.0333 AC XY: 5611 AN XY: 168500

Gnomad4 AFR exome AF: 0.00783 AC: 66 AN: 8432

Gnomad4 AMR exome AF: 0.0144 AC: 382 AN: 26448

Gnomad4 ASJ exome AF: 0.0371 AC: 374 AN: 10070

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 9202

Gnomad4 SAS exome AF: 0.0204 AC: 1197 AN: 58754

Gnomad4 FIN exome AF: 0.0540 AC: 648 AN: 12000

Gnomad4 NFE exome AF: 0.0448 AC: 6981 AN: 155886

Gnomad4 Remaining exome AF: 0.0346 AC: 475 AN: 13728

GnomAD4 genome AF: 0.0291 AC: 4352 AN: 149690 Hom.: 91 Cov.: 31 AF XY: 0.0288 AC XY: 2103 AN XY: 73124

Gnomad4 AFR AF: 0.00833 AC: 0.00833454 AN: 0.00833454

Gnomad4 AMR AF: 0.0207 AC: 0.020686 AN: 0.020686

Gnomad4 ASJ AF: 0.0354 AC: 0.0354354 AN: 0.0354354

Gnomad4 EAS AF: 0.000193 AC: 0.000192976 AN: 0.000192976

Gnomad4 SAS AF: 0.0196 AC: 0.019567 AN: 0.019567

Gnomad4 FIN AF: 0.0510 AC: 0.0509781 AN: 0.0509781

Gnomad4 NFE AF: 0.0435 AC: 0.0435298 AN: 0.0435298

Gnomad4 OTH AF: 0.0287 AC: 0.0286533 AN: 0.0286533

Alfa AF: 0.0305 Hom.: 56

Bravo AF: 0.0257

Asia WGS AF: 0.00983 AC: 34 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Mitochondrial complex III deficiency nuclear type 2 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely 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	-0.65
CADD	Benign	2.7
DANN	Benign	0.84
Mutation Taster		=100/0	polymorphism

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs117133932; hg19: chr17-15932425;