10-46549710-C-A

Variant names:

• chr10-46549710-C-A
• rs1555017873
• NM_001385282.1:c.1027G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001385282.1(GPRIN2):​c.1027G>T​(p.Ala343Ser) 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: 75)
• Consequence: GPRIN2 NM_001385282.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.93

Genes affected

GPRIN2 (HGNC:23730): (G protein regulated inducer of neurite outgrowth 2) Predicted to be involved in neuron projection development. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26090354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRIN2	NM_001385282.1	c.1027G>T	p.Ala343Ser	missense_variant	Exon 3 of 3	ENST00000374314.6	NP_001372211.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPRIN2	ENST00000374314.6	c.1027G>T	p.Ala343Ser	missense_variant	Exon 3 of 3	6	NM_001385282.1	ENSP00000363433.4
GPRIN2	ENST00000374317.2	c.1027G>T	p.Ala343Ser	missense_variant	Exon 3 of 3	3		ENSP00000363436.1

Frequencies

GnomAD3 genomes Cov.: 75

GnomAD4 exome Cov.: 140

GnomAD4 genome Cov.: 75

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 24, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1027G>T (p.A343S) alteration is located in exon 3 (coding exon 1) of the GPRIN2 gene. This alteration results from a G to T substitution at nucleotide position 1027, causing the alanine (A) at amino acid position 343 to be replaced by a serine (S). 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	0.14
BayesDel_noAF	Benign	-0.18
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T;T
LIST_S2	Benign	0.57	.;T
MetaRNN	Benign	0.26	T;T
PROVEAN	Benign	-1.6	N;N
Sift	Benign	0.19	T;T
Sift4G	Benign	0.41	T;T
Vest4		0.33
gMVP		0.25

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

LitVar

Other links and lift over

dbSNP: rs1555017873; hg19: chr10-46999907;