NM_001385282.1:c.571G>A

Variant names:

• chr10-46550166-C-T
• rs148885065
• NM_001385282.1:c.571G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001385282.1(GPRIN2):​c.571G>A​(p.Ala191Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000225 in 1,597,948 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A191V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000098 (0 hom., cov: 74)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: GPRIN2 NM_001385282.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0750
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08311644).

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.571G>A	p.Ala191Thr	missense	Exon 3 of 3	NP_001372211.1	O60269
	GPRIN2	NM_001385287.1		c.643G>A	p.Ala215Thr	missense	Exon 4 of 4	NP_001372216.1
	GPRIN2	NM_001385289.1		c.643G>A	p.Ala215Thr	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.571G>A	p.Ala191Thr	missense	Exon 3 of 3	ENSP00000363433.4	O60269
	GPRIN2	ENST00000374317.2	TSL:3	c.571G>A	p.Ala191Thr	missense	Exon 3 of 3	ENSP00000363436.1	O60269
	GPRIN2	ENST00000889306.1		c.571G>A	p.Ala191Thr	missense	Exon 4 of 4	ENSP00000559365.1

Frequencies

GnomAD3 genomes AF: 0.0000985 AC: 15 AN: 152296 Hom.: 0 Cov.: 74

Gnomad AFR AF: 0.000362

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: 0.0000288 AC: 7 AN: 242692 AF XY: 0.0000229

Gnomad AFR exome AF: 0.000310

Gnomad AMR exome AF: 0.0000589

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: 0.0000145 AC: 21 AN: 1445534 Hom.: 0 Cov.: 113 AF XY: 0.0000167 AC XY: 12 AN XY: 717182

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

African (AFR) AF: 0.000302 AC: 10 AN: 33090

American (AMR) AF: 0.0000455 AC: 2 AN: 43960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25346

East Asian (EAS) AF: 0.00 AC: 0 AN: 39434

South Asian (SAS) AF: 0.00 AC: 0 AN: 84484

European-Finnish (FIN) AF: 0.0000198 AC: 1 AN: 50564

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5696

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1103290

Other (OTH) AF: 0.0000670 AC: 4 AN: 59670

⚠️ 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: 0.0000984 AC: 15 AN: 152414 Hom.: 0 Cov.: 74 AF XY: 0.0000939 AC XY: 7 AN XY: 74540

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

African (AFR) AF: 0.000361 AC: 15 AN: 41594

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	Benign	0.071
BayesDel_noAF	Benign	-0.55
CADD	Benign	14
DANN	Benign	0.96
DEOGEN2	Benign	0.0021	T
LIST_S2	Benign	0.45	T
MetaRNN	Benign	0.083	T
PhyloP100		-0.075
PROVEAN	Benign	0.060	N
Sift	Benign	0.26	T
Sift4G	Benign	0.30	T
Vest4		0.054
gMVP		0.066

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: rs148885065; hg19: chr10-46999451;