rs1235128564

Variant names:

• chr19-17337612-A-C
• NM_032620.4:c.1A>C

Your query was ambiguous. Multiple possible variants found:

• chr19-17337612-A-C
• chr19-17337612-A-G
• chr19-17337612-A-T

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1 PS1_Moderate PM2

The NM_032620.4(GTPBP3):​c.1A>C​(p.Met1?) variant causes a initiator codon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000171 in 1,172,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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: 0.0000017 (0 hom.)
• Consequence: GTPBP3 NM_032620.4 initiator_codon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.57

Genes affected

GTPBP3 (HGNC:14880): (GTP binding protein 3, mitochondrial) This locus encodes a GTP-binding protein. The encoded protein is localized to the mitochondria and may play a role in mitochondrial tRNA modification. Polymorphisms at this locus may be associated with severity of aminoglycoside-induced deafness, a disease associated with a mutation in the 12S rRNA. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Pathogenic. Variant got 12 ACMG points.

• PVS1: Start lost variant, next in-frame start position is after 39 pathogenic variants. Next in-frame start position is after 335 codons. Genomic position: 17341072. Lost 0.678 part of the original CDS.
• PS1: Another start lost variant in NM_032620.4 (GTPBP3) was described as [Pathogenic] in ClinVar as 488854
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTPBP3	NM_032620.4	c.1A>C	p.Met1?	initiator_codon_variant	Exon 1 of 9	ENST00000324894.13	NP_116009.2
GTPBP3	NM_133644.4	c.1A>C	p.Met1?	initiator_codon_variant	Exon 1 of 8		NP_598399.2
GTPBP3	NM_001128855.3	c.1A>C	p.Met1?	initiator_codon_variant	Exon 1 of 9		NP_001122327.1
GTPBP3	NM_001195422.1	c.120-396A>C		intron_variant	Intron 1 of 8		NP_001182351.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTPBP3	ENST00000324894.13	c.1A>C	p.Met1?	initiator_codon_variant	Exon 1 of 9	1	NM_032620.4	ENSP00000313818.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000171 AC: 2 AN: 1172294 Hom.: 0 Cov.: 30 AF XY: 0.00000357 AC XY: 2 AN XY: 559654

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000359

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000104

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
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	21
DANN	Benign	0.92
DEOGEN2	Benign	0.032	T;.;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.016
FATHMM_MKL	Benign	0.55	D
LIST_S2	Uncertain	0.90	D;D;D
M_CAP	Uncertain	0.28	D
MetaRNN	Pathogenic	0.96	D;D;D
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-0.46	N;N;.
REVEL	Benign	0.25
Sift	Benign	0.22	T;T;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.0010	B;B;B
Vest4		0.85
MutPred		0.98		Loss of disorder (P = 0.3353);Loss of disorder (P = 0.3353);Loss of disorder (P = 0.3353);
MVP		0.31
ClinPred		0.99	D
GERP RS		3.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.37

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: chr19-17448421;