Variant 11-123608758-A-G 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.1613A>G(p.Asn538Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000005 in 1,400,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000050 ( 0 hom. )

Consequence

GRAMD1B
NM_001387025.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.64

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:

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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=0.10983577).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRAMD1B	NM_001387025.1 linkuse as main transcript	c.1613A>G	p.Asn538Ser	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 linkuse as main transcript	c.1613A>G	p.Asn538Ser	missense_variant	12/20	5	NM_001387025.1	ENSP00000490062	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000500

AC:

AN:

1400058

Hom.:

Cov.:

AF XY:

0.00000434

AC XY:

AN XY:

690546

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000649

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jun 10, 2024

The c.1184A>G (p.N395S) alteration is located in exon 11 (coding exon 11) of the GRAMD1B gene. This alteration results from a A to G substitution at nucleotide position 1184, causing the asparagine (N) at amino acid position 395 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

0.071

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.020

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

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.72

T;T;T;T;T;T;T;T;T;D

M_CAP

Benign

0.0046

MetaRNN

Benign

0.11

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

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.98

N;N;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.48

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

REVEL

Benign

0.057

Sift

Benign

0.28

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

Sift4G

Benign

0.44

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

Polyphen

0.0050, 0.0040

.;.;.;.;.;B;.;.;.;B

Vest4

0.22, 0.25, 0.27, 0.27, 0.10

MutPred

0.55

.;.;.;Gain of disorder (P = 0.0551);.;.;.;.;.;.;

MVP

0.082

MPC

0.29

ClinPred

0.63

GERP RS

1.7

Varity_R

0.042

gMVP

0.20

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over