Genetic Variant NM_001009184.2:c.9T>A (chr8-143991232-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001009184.2(GRINA):c.9T>A(p.His3Gln) 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. 15/22 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. H3R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

GRINA
NM_001009184.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.809

Publications

0 publications found

Variant links:

Genes affected

GRINA (HGNC:4589): (glutamate ionotropic receptor NMDA type subunit associated protein 1) Predicted to enable transmembrane transporter binding activity. Predicted to act upstream of or within endoplasmic reticulum calcium ion homeostasis and negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway. Predicted to be located in Golgi apparatus and endoplasmic reticulum. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

GRINA links:

PARP10 (HGNC:25895): (poly(ADP-ribose) polymerase family member 10) Poly(ADP-ribose) polymerases (PARPs), such as PARP10, regulate gene transcription by altering chromatin organization by adding ADP-ribose to histones. PARPs can also function as transcriptional cofactors (Yu et al., 2005 [PubMed 15674325]).[supplied by OMIM, Mar 2008]

PARP10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049383134).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009184.2. 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
	GRINA	NM_001009184.2	MANE Select	c.9T>A	p.His3Gln	missense	Exon 2 of 7	NP_001009184.1	Q7Z429
	GRINA	NM_000837.2		c.9T>A	p.His3Gln	missense	Exon 2 of 7	NP_000828.1	Q7Z429

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRINA	ENST00000395068.9	TSL:1 MANE Select	c.9T>A	p.His3Gln	missense	Exon 2 of 7	ENSP00000378507.4	Q7Z429
GRINA	ENST00000857587.1		c.9T>A	p.His3Gln	missense	Exon 2 of 6	ENSP00000527646.1
GRINA	ENST00000857582.1		c.9T>A	p.His3Gln	missense	Exon 2 of 7	ENSP00000527641.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.9

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.18

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.59

M_CAP

Benign

0.026

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.20

PhyloP100

-0.81

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-1.0

REVEL

Benign

0.039

Sift

Benign

0.15

Sift4G

Benign

0.25

Polyphen

0.075

Vest4

0.25

MutPred

0.23

Gain of solvent accessibility (P = 0.0766)

MVP

0.068

MPC

0.0074

ClinPred

0.029

GERP RS

0.033

PromoterAI

0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.20

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over