9-137158422-G-C

Variant names:

• chr9-137158422-G-C
• NM_007327.4:c.1012G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2 PP2 BP4 BP6_Moderate

The NM_007327.4(GRIN1):​c.1012G>C​(p.Val338Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GRIN1 NM_007327.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.35

Genes affected

GRIN1 (HGNC:4584): (glutamate ionotropic receptor NMDA type subunit 1) The protein encoded by this gene is a critical subunit of N-methyl-D-aspartate receptors, members of the glutamate receptor channel superfamily which are heteromeric protein complexes with multiple subunits arranged to form a ligand-gated ion channel. These subunits play a key role in the plasticity of synapses, which is believed to underlie memory and learning. Cell-specific factors are thought to control expression of different isoforms, possibly contributing to the functional diversity of the subunits. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2008]

LOC105376328 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in the GRIN1 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 75 curated pathogenic missense variants (we use a threshold of 10). The gene has 49 curated benign missense variants. Gene score misZ: 6.2157 (above the threshold of 3.09). Trascript score misZ: 6.6419 (above the threshold of 3.09). GenCC associations: The gene is linked to developmental and epileptic encephalopathy 101, neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive, autosomal dominant non-syndromic intellectual disability, complex neurodevelopmental disorder, intellectual disability, autosomal dominant 8.
• BP4: Computational evidence support a benign effect (MetaRNN=0.36103445).
• BP6: Variant 9-137158422-G-C is Benign according to our data. Variant chr9-137158422-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1655991.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN1	NM_007327.4	c.1012G>C	p.Val338Leu	missense_variant	Exon 7 of 20	ENST00000371561.8	NP_015566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN1	ENST00000371561.8	c.1012G>C	p.Val338Leu	missense_variant	Exon 7 of 20	1	NM_007327.4	ENSP00000360616.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, autosomal dominant 8 Benign:1

Jan 14, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	0.97
DEOGEN2	Uncertain	0.43	T;.;.;T;.;.;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.88	D;D;D;D;D;D;D
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.36	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L;.;.;.;L;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-2.3	N;N;N;N;N;N;N
REVEL	Benign	0.18
Sift	Benign	0.47	T;T;T;T;T;T;T
Sift4G	Benign	0.10	T;T;T;T;T;T;T
Polyphen		0.064	B;B;.;.;.;B;.
Vest4		0.35
MutPred		0.80		Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);.;.;.;Loss of sheet (P = 0.0817);.;
MVP		0.77
MPC		1.3
ClinPred		0.54	D
GERP RS		4.0
Varity_R		0.32
gMVP		0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-140052874;