NM_001009184.2:c.9T>C

Variant names:

• chr8-143991232-T-C
• rs1554750370
• NM_001009184.2:c.9T>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001009184.2(GRINA):​c.9T>C​(p.His3His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000491 in 1,426,432 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: GRINA NM_001009184.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.809
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-0.809 with no splicing effect.

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>C	p.His3His	synonymous	Exon 2 of 7	NP_001009184.1	Q7Z429
	GRINA	NM_000837.2		c.9T>C	p.His3His	synonymous	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.9T>C	p.His3His	synonymous	Exon 2 of 7	ENSP00000378507.4	Q7Z429
	GRINA	ENST00000857587.1		c.9T>C	p.His3His	synonymous	Exon 2 of 6	ENSP00000527646.1
	GRINA	ENST00000857582.1		c.9T>C	p.His3His	synonymous	Exon 2 of 7	ENSP00000527641.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 219396 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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: 0.00000491 AC: 7 AN: 1426432 Hom.: 0 Cov.: 27 AF XY: 0.00000282 AC XY: 2 AN XY: 709754

African (AFR) AF: 0.00 AC: 0 AN: 31504

American (AMR) AF: 0.00 AC: 0 AN: 39180

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24286

East Asian (EAS) AF: 0.00 AC: 0 AN: 36976

South Asian (SAS) AF: 0.00 AC: 0 AN: 82292

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52562

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 0.00000548 AC: 6 AN: 1095278

Other (OTH) AF: 0.0000170 AC: 1 AN: 58746

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.3
DANN	Benign	0.76
PhyloP100		-0.81
PromoterAI		0.0074	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1554750370; hg19: chr8-145065400;