chr10-46549535-T-C

Variant names:

• chr10-46549535-T-C
• rs149433440
• NM_001385282.1:c.1202A>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001385282.1(GPRIN2):​c.1202A>G​(p.Glu401Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000663 in 1,613,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 79)
  • Exomes 𝑓: 0.000038 (0 hom.)
• Consequence: GPRIN2 NM_001385282.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.93
• Publications: 2 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.748

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385282.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRIN2	NM_001385282.1	MANE Select	c.1202A>G	p.Glu401Gly	missense	Exon 3 of 3	NP_001372211.1	O60269
	GPRIN2	NM_001385287.1		c.1274A>G	p.Glu425Gly	missense	Exon 4 of 4	NP_001372216.1
	GPRIN2	NM_001385289.1		c.1274A>G	p.Glu425Gly	missense	Exon 4 of 4	NP_001372218.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPRIN2	ENST00000374314.6	TSL:6 MANE Select	c.1202A>G	p.Glu401Gly	missense	Exon 3 of 3	ENSP00000363433.4	O60269
	GPRIN2	ENST00000374317.2	TSL:3	c.1202A>G	p.Glu401Gly	missense	Exon 3 of 3	ENSP00000363436.1	O60269
	GPRIN2	ENST00000889306.1		c.1202A>G	p.Glu401Gly	missense	Exon 4 of 4	ENSP00000559365.1

Frequencies

GnomAD3 genomes AF: 0.000341 AC: 52 AN: 152270 Hom.: 0 Cov.: 79

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000638 AC: 16 AN: 250616 AF XY: 0.0000517

Gnomad AFR exome AF: 0.000925

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000376 AC: 55 AN: 1461104 Hom.: 0 Cov.: 120 AF XY: 0.0000358 AC XY: 26 AN XY: 726784

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00144 AC: 48 AN: 33424

American (AMR) AF: 0.0000224 AC: 1 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39678

South Asian (SAS) AF: 0.00 AC: 0 AN: 86184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111550

Other (OTH) AF: 0.0000497 AC: 3 AN: 60340

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000341 AC: 52 AN: 152388 Hom.: 0 Cov.: 79 AF XY: 0.000362 AC XY: 27 AN XY: 74524

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00125 AC: 52 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15314

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68050

Other (OTH) AF: 0.00 AC: 0 AN: 2116

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000843 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_noAF	Pathogenic	0.23
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
LIST_S2	Uncertain	0.93	D
MetaRNN	Pathogenic	0.75	D
PhyloP100		4.9
PROVEAN	Pathogenic	-7.0	D
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Vest4		0.67
gMVP		0.85

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

Other links and lift over

dbSNP: rs149433440; hg19: chr10-47000082;