13-113325704-A-G

Position:

• chr13-113325704-A-G

Variant summary

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

The NM_024719.4(GRTP1):​c.878T>C​(p.Ile293Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GRTP1 NM_024719.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.38

Genes affected

GRTP1 (HGNC:20310): (growth hormone regulated TBC protein 1) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. [provided by Alliance of Genome Resources, Apr 2022]

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
GRTP1	NM_024719.4	c.878T>C	p.Ile293Thr	missense_variant	7/8	ENST00000375431.9
GRTP1	NM_001286732.2	c.878T>C	p.Ile293Thr	missense_variant	7/7
GRTP1	NM_001411029.1	c.644T>C	p.Ile215Thr	missense_variant	7/7
GRTP1	NM_001286733.1	c.563-1127T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GRTP1	ENST00000375431.9	c.878T>C	p.Ile293Thr	missense_variant	7/8	1	NM_024719.4	P1
GRTP1	ENST00000375430.8	c.878T>C	p.Ile293Thr	missense_variant	7/7	1
GRTP1	ENST00000326039.3	c.644T>C	p.Ile215Thr	missense_variant	5/5	1
GRTP1	ENST00000620217.4	c.563-1127T>C		intron_variant		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

Jun 02, 2023

The c.878T>C (p.I293T) alteration is located in exon 7 (coding exon 7) of the GRTP1 gene. This alteration results from a T to C substitution at nucleotide position 878, causing the isoleucine (I) at amino acid position 293 to be replaced by a threonine (T). 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	Pathogenic	0.77
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.055	T;.;.
Eigen	Uncertain	0.26
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;D;D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.72	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.1	M;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-4.1	D;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0030	D;D;D
Sift4G	Uncertain	0.0050	D;D;T
Polyphen		0.87	P;.;.
Vest4		0.82
MutPred		0.60		Loss of stability (P = 0.025);Loss of stability (P = 0.025);.;
MVP		0.41
MPC		0.39
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.48
gMVP		0.65

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: chr13-113980019;