rs756830714

Variant names:

• chr17-15999855-C-G
• rs756830714
• NM_017775.4:c.7C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-15999855-C-G
• chr17-15999855-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2 PM5 BP4

The NM_017775.4(TTC19):​c.7C>G​(p.Arg3Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3W) has been classified as Likely pathogenic.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TTC19 NM_017775.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.514

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr17-15999855-C-T is described in Lovd as [Likely_pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.3266104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC19	NM_017775.4	c.7C>G	p.Arg3Gly	missense_variant	Exon 1 of 10	ENST00000261647.10	NP_060245.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC19	ENST00000261647.10	c.7C>G	p.Arg3Gly	missense_variant	Exon 1 of 10	1	NM_017775.4	ENSP00000261647.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1362824 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 671918

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.014	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	17
DANN	Benign	0.62
DEOGEN2	Benign	0.0078	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.35	T
M_CAP	Pathogenic	0.84	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.90	L
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-0.44	N
REVEL	Uncertain	0.33
Sift	Benign	0.34	T
Sift4G	Benign	0.48	T
Vest4		0.45
MutPred		0.35		Loss of stability (P = 0.0278);
MVP		0.46
MPC		0.18
ClinPred		0.20	T
GERP RS		-1.4
Varity_R		0.090
gMVP		0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs756830714; hg19: chr17-15903169;