17-15999798-G-T

Variant names:

• chr17-15999798-G-T
• rs1319527245
• ENST00000918096.1:c.-51G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000918096.1(TTC19):​c.-51G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000356 in 1,406,138 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: TTC19 ENST00000918096.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.881
• Publications: 0 publications found

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]

ZSWIM7 (HGNC:26993): (zinc finger SWIM-type containing 7) Predicted to enable zinc ion binding activity. Involved in double-strand break repair via homologous recombination and protein stabilization. Part of Shu complex. [provided by Alliance of Genome Resources, Apr 2022]

ZSWIM7 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: STRONG Submitted by: King Faisal Specialist Hospital and Research Center
• ovarian dysgenesis 10

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• colorectal adenoma

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.042).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000918096.1. 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
	TTC19	NM_017775.4	MANE Select	c.-51G>T		upstream_gene	N/A	NP_060245.3
	ZSWIM7	NM_001042697.2	MANE Select	c.-204C>A		upstream_gene	N/A	NP_001036162.1	Q19AV6
	TTC19	NM_001271420.2		c.-509G>T		upstream_gene	N/A	NP_001258349.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC19	ENST00000918096.1		c.-51G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 10	ENSP00000588155.1
	TTC19	ENST00000873204.1		c.-51G>T		5_prime_UTR	Exon 1 of 10	ENSP00000543263.1
	TTC19	ENST00000918096.1		c.-51G>T		5_prime_UTR	Exon 1 of 10	ENSP00000588155.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000356 AC: 5 AN: 1406138 Hom.: 0 Cov.: 30 AF XY: 0.00000431 AC XY: 3 AN XY: 696368

African (AFR) AF: 0.00 AC: 0 AN: 32474

American (AMR) AF: 0.00 AC: 0 AN: 38366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25242

East Asian (EAS) AF: 0.0000266 AC: 1 AN: 37658

South Asian (SAS) AF: 0.00 AC: 0 AN: 80566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5310

European-Non Finnish (NFE) AF: 0.00000275 AC: 3 AN: 1091282

Other (OTH) AF: 0.0000171 AC: 1 AN: 58642

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.9
DANN	Benign	0.91
PhyloP100		-0.88
PromoterAI		0.028	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1319527245; hg19: chr17-15903112;