11-123577563-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001387025.1(GRAMD1B):​c.649G>A​(p.Gly217Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000252 in 1,586,236 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: 0.0000021 ( 0 hom. )

Consequence

GRAMD1B
NM_001387025.1 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.37
Variant links:
Genes affected
GRAMD1B (HGNC:29214): (GRAM domain containing 1B) Predicted to enable cholesterol binding activity; cholesterol transfer activity; and phospholipid binding activity. Predicted to be involved in cellular response to cholesterol and cholesterol homeostasis. Located in endoplasmic reticulum membrane; endoplasmic reticulum-plasma membrane contact site; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08890298).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GRAMD1BNM_001387025.1 linkuse as main transcriptc.649G>A p.Gly217Ser missense_variant 3/20 ENST00000635736.2 NP_001373954.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GRAMD1BENST00000635736.2 linkuse as main transcriptc.649G>A p.Gly217Ser missense_variant 3/205 NM_001387025.1 ENSP00000490062 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152246
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000511
AC:
1
AN:
195654
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
106232
show subpopulations
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 SAS exome
AF:
0.0000396
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000209
AC:
3
AN:
1433990
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
710986
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000122
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000182
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152246
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000833
AC:
1

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 GeneticsJan 09, 2024The c.220G>A (p.G74S) alteration is located in exon 2 (coding exon 2) of the GRAMD1B gene. This alteration results from a G to A substitution at nucleotide position 220, causing the glycine (G) at amino acid position 74 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
Benign
0.069
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.0040
T;T;.;.;T;.;.;T;T;.;.
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.073
FATHMM_MKL
Benign
0.69
D
LIST_S2
Uncertain
0.87
D;D;T;T;D;T;D;D;D;D;D
M_CAP
Benign
0.0073
T
MetaRNN
Benign
0.089
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-0.43
.;.;.;.;.;.;N;N;N;N;N
REVEL
Benign
0.050
Sift
Benign
0.13
.;.;.;.;.;.;T;T;T;T;T
Sift4G
Benign
0.75
.;.;T;T;.;T;T;T;T;T;T
Polyphen
0.019
.;.;.;.;.;.;.;.;B;.;.
Vest4
0.14, 0.16, 0.14, 0.16
MutPred
0.26
.;.;.;.;.;.;Gain of phosphorylation at G74 (P = 0.0019);Gain of phosphorylation at G74 (P = 0.0019);Gain of phosphorylation at G74 (P = 0.0019);.;.;
MVP
0.043
MPC
1.6
ClinPred
0.39
T
GERP RS
3.5
Varity_R
0.089
gMVP
0.39

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: rs767530052; hg19: chr11-123448271; API