11-123577441-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001387025.1(GRAMD1B):​c.527C>G​(p.Pro176Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,450,634 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P176Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

GRAMD1B
NM_001387025.1 missense

Scores

7
11

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.54
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38049835).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRAMD1BNM_001387025.1 linkc.527C>G p.Pro176Arg missense_variant Exon 3 of 20 ENST00000635736.2 NP_001373954.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRAMD1BENST00000635736.2 linkc.527C>G p.Pro176Arg missense_variant Exon 3 of 20 5 NM_001387025.1 ENSP00000490062.1 A0A1B0GUD6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1450634
Hom.:
0
Cov.:
32
AF XY:
0.00000139
AC XY:
1
AN XY:
720414
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000256
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.03e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.21
BayesDel_addAF
Uncertain
0.072
D
BayesDel_noAF
Benign
-0.13
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.031
T;.;T;.;T;T;.
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Uncertain
0.91
D;D;D;D;D;D;D
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.38
T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-1.8
.;.;.;N;N;N;N
REVEL
Benign
0.20
Sift
Benign
0.068
.;.;.;T;D;D;D
Sift4G
Benign
0.076
.;T;.;T;T;T;D
Polyphen
0.93
.;.;.;.;.;P;.
Vest4
0.59, 0.49, 0.44
MutPred
0.36
.;.;.;Gain of MoRF binding (P = 5e-04);Gain of MoRF binding (P = 5e-04);Gain of MoRF binding (P = 5e-04);.;
MVP
0.068
MPC
2.3
ClinPred
0.90
D
GERP RS
4.9
Varity_R
0.25
gMVP
0.70

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: chr11-123448149; API