13-113326014-C-G

Position:

• chr13-113326014-C-G

Variant summary

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

The NM_024719.4(GRTP1):​c.640G>C​(p.Ala214Pro) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: GRTP1 NM_024719.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.47

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32887107).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRTP1	NM_024719.4	c.640G>C	p.Ala214Pro	missense_variant	6/8	ENST00000375431.9	NP_078995.2
GRTP1	NM_001286732.2	c.640G>C	p.Ala214Pro	missense_variant	6/7		NP_001273661.1
GRTP1	NM_001411029.1	c.406G>C	p.Ala136Pro	missense_variant	6/7		NP_001397958.1
GRTP1	NM_001286733.1	c.563-1437G>C		intron_variant			NP_001273662.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRTP1	ENST00000375431.9	c.640G>C	p.Ala214Pro	missense_variant	6/8	1	NM_024719.4	ENSP00000364580	P1
GRTP1	ENST00000375430.8	c.640G>C	p.Ala214Pro	missense_variant	6/7	1		ENSP00000364579
GRTP1	ENST00000326039.3	c.406G>C	p.Ala136Pro	missense_variant	4/5	1		ENSP00000321850
GRTP1	ENST00000620217.4	c.563-1437G>C		intron_variant		2		ENSP00000483734

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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

May 15, 2023

The c.640G>C (p.A214P) alteration is located in exon 6 (coding exon 6) of the GRTP1 gene. This alteration results from a G to C substitution at nucleotide position 640, causing the alanine (A) at amino acid position 214 to be replaced by a proline (P). 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	Benign	0.15
BayesDel_addAF	Benign	0.0093	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T;.;.
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.33	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L;L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.3	N;N;N
REVEL	Benign	0.16
Sift	Benign	0.26	T;T;T
Sift4G	Benign	0.23	T;T;T
Polyphen		0.095	B;.;B
Vest4		0.39
MutPred		0.52		Gain of catalytic residue at V215 (P = 0);Gain of catalytic residue at V215 (P = 0);.;
MVP		0.21
MPC		0.19
ClinPred		0.82	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.65
gMVP		0.83

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: chr13-113980329;