chr17-15999897-G-T

Variant names:

• chr17-15999897-G-T
• NM_017775.4:c.49G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017775.4(TTC19):​c.49G>T​(p.Ala17Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000803 in 1,245,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: TTC19 NM_017775.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.277

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28630418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTC19	NM_017775.4	c.49G>T	p.Ala17Ser	missense_variant	Exon 1 of 10	ENST00000261647.10	NP_060245.3
ZSWIM7	NM_001042697.2	c.-303C>A		upstream_gene_variant		ENST00000399277.6	NP_001036162.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTC19	ENST00000261647.10	c.49G>T	p.Ala17Ser	missense_variant	Exon 1 of 10	1	NM_017775.4	ENSP00000261647.5
ZSWIM7	ENST00000399277.6	c.-303C>A		upstream_gene_variant		1	NM_001042697.2	ENSP00000382218.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.03e-7 AC: 1 AN: 1245370 Hom.: 0 Cov.: 30 AF XY: 0.00000165 AC XY: 1 AN XY: 605092

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: 9.83e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.011	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	13
DANN	Benign	0.82
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Benign	0.81	L
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.14
Sift	Benign	0.032	D
Sift4G	Pathogenic	0.0	D
Vest4		0.32
MutPred		0.34		Gain of phosphorylation at A17 (P = 0.0037);
MVP		0.79
MPC		0.12
ClinPred		0.10	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.062
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-15903211;