22-38716826-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004286.5(GTPBP1):c.660T>G(p.Ser220Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GTPBP1 NM_004286.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.48

Genes affected

GTPBP1 (HGNC:4669): (GTP binding protein 1) This gene is upregulated by interferon-gamma and encodes a protein that is a member of the AGP11/GTPBP1 family of GTP-binding proteins. A structurally similar protein has been found in mouse, where disruption of the gene for that protein had no observable phenotype. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTPBP1	NM_004286.5	c.660T>G	p.Ser220Arg	missense_variant	4/12	ENST00000216044.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTPBP1	ENST00000216044.10	c.660T>G	p.Ser220Arg	missense_variant	4/12	1	NM_004286.5	P1
GTPBP1	ENST00000484657.5	c.417T>G	p.Ser139Arg	missense_variant	4/4	4
GTPBP1	ENST00000418601.1	c.*335T>G		3_prime_UTR_variant, NMD_transcript_variant	3/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2022

The c.660T>G (p.S220R) alteration is located in exon 4 (coding exon 4) of the GTPBP1 gene. This alteration results from a T to G substitution at nucleotide position 660, causing the serine (S) at amino acid position 220 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	18
Dann	Uncertain	0.98
DEOGEN2	Uncertain	0.58	D;T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.25	N
LIST_S2	Uncertain	0.95	D;D
M_CAP	Uncertain	0.092	D
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.67	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	0.99	D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.4	D;D
REVEL	Uncertain	0.30
Sift	Benign	0.051	T;D
Sift4G	Uncertain	0.022	D;T
Polyphen		0.59	P;.
Vest4		0.27
MutPred		0.50		Loss of phosphorylation at S220 (P = 0.0808);.;
MVP		0.47
MPC		1.9
ClinPred		0.98	D
GERP RS		-8.4
Varity_R		0.52
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.32		Position offset: 0

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: chr22-39112831;