dbSNP rs756954687: GPRIN3:p.Lys539* (chr4-89248496-T-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_198281.3(GPRIN3):c.1615A>T(p.Lys539*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,572 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GPRIN3
NM_198281.3 stop_gained

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0830

Publications

0 publications found

Variant links:

Genes affected

GPRIN3 (HGNC:27733): (GPRIN family member 3) Predicted to be involved in neuron projection development. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPRIN3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPRIN3	NM_198281.3 link	c.1615A>T	p.Lys539*	stop_gained	Exon 2 of 2	ENST00000609438.2	NP_938022.2	Q6ZVF9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GPRIN3	ENST00000609438.2 link	c.1615A>T	p.Lys539*	stop_gained	Exon 2 of 2	2	NM_198281.3	ENSP00000476603.1	Q6ZVF9
GPRIN3	ENST00000333209.4 link	c.1615A>T	p.Lys539*	stop_gained	Exon 1 of 1	6		ENSP00000328672.3	Q6ZVF9
GPRIN3	ENST00000715382.1 link	c.1615A>T	p.Lys539*	stop_gained	Exon 2 of 2			ENSP00000520450.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460572

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726468

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33350

American (AMR)

AF:

0.00

AC:

AN:

44548

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39680

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111394

Other (OTH)

AF:

0.00

AC:

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.27

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.017

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.22

PhyloP100

-0.083

Vest4

0.042

GERP RS

2.4

Mutation Taster

=21/179

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over