chr19-1000567-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_138690.3(GRIN3B):​c.130C>T​(p.Pro44Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00166 in 1,058,698 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00097 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0018 ( 5 hom. )

Consequence

GRIN3B
NM_138690.3 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52
Variant links:
Genes affected
GRIN3B (HGNC:16768): (glutamate ionotropic receptor NMDA type subunit 3B) The protein encoded by this gene is a subunit of an N-methyl-D-aspartate (NMDA) receptor. The encoded protein is found primarily in motor neurons, where it forms a heterotetramer with GRIN1 to create an excitatory glycine receptor. Variations in this gene have been proposed to be linked to schizophrenia. [provided by RefSeq, Nov 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.3121369).
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GRIN3BNM_138690.3 linkuse as main transcriptc.130C>T p.Pro44Ser missense_variant 1/9 ENST00000234389.3 NP_619635.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GRIN3BENST00000234389.3 linkuse as main transcriptc.130C>T p.Pro44Ser missense_variant 1/91 NM_138690.3 ENSP00000234389 P1
ENST00000588380.1 linkuse as main transcriptn.270-400G>A intron_variant, non_coding_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.000972
AC:
143
AN:
147130
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000171
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00176
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000115
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00163
Gnomad OTH
AF:
0.000492
GnomAD4 exome
AF:
0.00177
AC:
1616
AN:
911460
Hom.:
5
Cov.:
32
AF XY:
0.00176
AC XY:
751
AN XY:
427142
show subpopulations
Gnomad4 AFR exome
AF:
0.000285
Gnomad4 AMR exome
AF:
0.000302
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000389
Gnomad4 FIN exome
AF:
0.000247
Gnomad4 NFE exome
AF:
0.00189
Gnomad4 OTH exome
AF:
0.00207
GnomAD4 genome
AF:
0.000971
AC:
143
AN:
147238
Hom.:
0
Cov.:
33
AF XY:
0.000920
AC XY:
66
AN XY:
71726
show subpopulations
Gnomad4 AFR
AF:
0.000171
Gnomad4 AMR
AF:
0.00175
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000115
Gnomad4 NFE
AF:
0.00163
Gnomad4 OTH
AF:
0.000487
Alfa
AF:
0.00244
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 13, 2021The c.130C>T (p.P44S) alteration is located in exon 1 (coding exon 1) of the GRIN3B gene. This alteration results from a C to T substitution at nucleotide position 130, causing the proline (P) at amino acid position 44 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.51
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Uncertain
26
DANN
Uncertain
1.0
DEOGEN2
Benign
0.051
T
Eigen
Benign
0.13
Eigen_PC
Benign
0.046
FATHMM_MKL
Benign
0.32
N
LIST_S2
Benign
0.59
T
M_CAP
Uncertain
0.22
D
MetaRNN
Benign
0.31
T
MetaSVM
Benign
-0.86
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
0.64
N
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.096
Sift
Benign
0.28
T
Sift4G
Benign
0.062
T
Polyphen
1.0
D
Vest4
0.36
MVP
0.64
MPC
0.15
ClinPred
0.91
D
GERP RS
2.3
Varity_R
0.069
gMVP
0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1037006531; hg19: chr19-1000566; API