rs143329355

Variant names:

• chr8-143991290-G-T
• rs143329355
• NM_001009184.2:c.67G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-143991290-G-T
• chr8-143991290-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001009184.2(GRINA):​c.67G>T​(p.Gly23Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 151,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GRINA NM_001009184.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.16
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23481548).

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.67G>T	p.Gly23Trp	missense	Exon 2 of 7	NP_001009184.1	Q7Z429
	GRINA	NM_000837.2		c.67G>T	p.Gly23Trp	missense	Exon 2 of 7	NP_000828.1	Q7Z429

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRINA	ENST00000395068.9	TSL:1 MANE Select	c.67G>T	p.Gly23Trp	missense	Exon 2 of 7	ENSP00000378507.4	Q7Z429
	GRINA	ENST00000857587.1		c.67G>T	p.Gly23Trp	missense	Exon 2 of 6	ENSP00000527646.1
	GRINA	ENST00000857582.1		c.67G>T	p.Gly23Trp	missense	Exon 2 of 7	ENSP00000527641.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151902 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1342822 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 668272

African (AFR) AF: 0.00 AC: 0 AN: 29174

American (AMR) AF: 0.00 AC: 0 AN: 31286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21240

East Asian (EAS) AF: 0.00 AC: 0 AN: 36356

South Asian (SAS) AF: 0.00 AC: 0 AN: 74600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50976

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5334

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1038258

Other (OTH) AF: 0.00 AC: 0 AN: 55598

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151902 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74190

African (AFR) AF: 0.00 AC: 0 AN: 41316

American (AMR) AF: 0.00 AC: 0 AN: 15272

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67910

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000826 AC: 1

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	0.40
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	27
DANN	Benign	0.96
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		6.2
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.043
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.011	D
Polyphen		0.95	P
Vest4		0.39
MVP		0.043
MPC		0.0071
ClinPred		0.72	D
GERP RS		5.1
PromoterAI		-0.058	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.8
Varity_R		0.13
gMVP		0.26
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs143329355; hg19: chr8-145065458;