Variant 11-123608773-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001387025.1(GRAMD1B):c.1628G>A(p.Arg543Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000342 in 1,551,230 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 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

GRAMD1B
NM_001387025.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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]

GRAMD1B links:

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=0.109454244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRAMD1B	NM_001387025.1 link	c.1628G>A	p.Arg543Gln	missense_variant	12/20	ENST00000635736.2	NP_001373954.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRAMD1B	ENST00000635736.2 link	c.1628G>A	p.Arg543Gln	missense_variant	12/20	5	NM_001387025.1	ENSP00000490062.1		A0A1B0GUD6

Frequencies

GnomAD3 genomes

AF:

0.0000854

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000375

AC:

AN:

159866

Hom.:

AF XY:

0.0000239

AC XY:

AN XY:

83614

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000404

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000915

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000638

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000286

AC:

AN:

1399082

Hom.:

Cov.:

AF XY:

0.0000188

AC XY:

AN XY:

690034

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.0000253

Gnomad4 FIN exome

AF:

0.0000202

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000854

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.000217

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000823

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000127

AC:

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 submitter

clinical testing

Ambry Genetics

Oct 30, 2023

The c.1199G>A (p.R400Q) alteration is located in exon 11 (coding exon 11) of the GRAMD1B gene. This alteration results from a G to A substitution at nucleotide position 1199, causing the arginine (R) at amino acid position 400 to be replaced by a glutamine (Q). 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

0.067

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.39

CADD

Pathogenic

DANN

Benign

0.89

DEOGEN2

Benign

0.0036

T;T;T;.;T;T;.;.;.;.

Eigen

Benign

-0.077

Eigen_PC

Benign

0.14

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.11

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.54

PROVEAN

Benign

1.0

.;.;.;N;N;N;N;N;.;N

REVEL

Benign

0.18

Sift

Benign

1.0

.;.;.;T;T;T;T;T;.;T

Sift4G

Benign

1.0

.;.;.;T;T;T;T;T;.;T

Polyphen

0.071, 1.0

.;.;.;.;.;B;.;.;.;D

Vest4

0.18, 0.18, 0.16, 0.16, 0.093

MutPred

0.34

.;.;.;Gain of disorder (P = 0.1564);.;.;.;.;.;.;

MVP

0.19

MPC

0.56

ClinPred

0.063

GERP RS

5.5

Varity_R

0.097

gMVP

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over