chr22-38716788-A-G

Position:

• chr22-38716788-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_004286.5(GTPBP1):​c.622A>G​(p.Thr208Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GTPBP1 NM_004286.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 9.17

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 Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.948
• PP5: Variant 22-38716788-A-G is Pathogenic according to our data. Variant chr22-38716788-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 3338052.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTPBP1	NM_004286.5	c.622A>G	p.Thr208Ala	missense_variant	4/12	ENST00000216044.10	NP_004277.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTPBP1	ENST00000216044.10	c.622A>G	p.Thr208Ala	missense_variant	4/12	1	NM_004286.5	ENSP00000216044.5
GTPBP1	ENST00000484657.5	c.379A>G	p.Thr127Ala	missense_variant	4/4	4		ENSP00000442881.1
GTPBP1	ENST00000418601.1	n.*297A>G		non_coding_transcript_exon_variant	3/4	2		ENSP00000397891.1
GTPBP1	ENST00000418601.1	n.*297A>G		3_prime_UTR_variant	3/4	2		ENSP00000397891.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 23, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	30
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.95	D;D
MetaSVM	Uncertain	0.40	D
MutationAssessor	Pathogenic	3.0	M;.
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Pathogenic	0.83
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.95	P;.
Vest4		0.87
MutPred		0.87		Loss of glycosylation at T208 (P = 0.1103);.;
MVP		0.80
MPC		1.7
ClinPred		0.99	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.79
gMVP		0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr22-39112793;