Variant 19-35013606-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_020895.5(GRAMD1A):c.785G>A(p.Arg262His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00359 in 1,613,482 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0037 ( 27 hom. )

Consequence

GRAMD1A
NM_020895.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.51

Variant links:

Genes affected

GRAMD1A (HGNC:29305): (GRAM domain containing 1A) Predicted to enable cholesterol binding activity and cholesterol transfer activity. Predicted to be involved in cellular response to cholesterol. Located in cytosol; organelle membrane contact site; and plasma membrane. Is extrinsic component of cytoplasmic side of plasma membrane and intrinsic component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

GRAMD1A links:

GRAMD1A (HGNC:):

GRAMD1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003685385).

BP6

Variant 19-35013606-G-A is Benign according to our data. Variant chr19-35013606-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2649712.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRAMD1A	NM_020895.5 linkuse as main transcript	c.785G>A	p.Arg262His	missense_variant	9/20	ENST00000317991.10	NP_065946.2	Q96CP6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRAMD1A	ENST00000317991.10 linkuse as main transcript	c.785G>A	p.Arg262His	missense_variant	9/20	1	NM_020895.5	ENSP00000441032.1		Q96CP6-1

Frequencies

GnomAD3 genomes

AF:

0.00256

AC:

390

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00398

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00242

AC:

598

AN:

247480

Hom.:

AF XY:

0.00245

AC XY:

330

AN XY:

134622

show subpopulations

Gnomad AFR exome

AF:

0.000926

Gnomad AMR exome

AF:

0.00215

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000884

Gnomad FIN exome

AF:

0.00140

Gnomad NFE exome

AF:

0.00390

Gnomad OTH exome

AF:

0.00266

GnomAD4 exome

AF:

0.00370

AC:

5406

AN:

1461160

Hom.:

Cov.:

AF XY:

0.00372

AC XY:

2701

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.000657

Gnomad4 AMR exome

AF:

0.00192

Gnomad4 ASJ exome

AF:

0.000115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00103

Gnomad4 FIN exome

AF:

0.00118

Gnomad4 NFE exome

AF:

0.00445

Gnomad4 OTH exome

AF:

0.00316

GnomAD4 genome

AF:

0.00256

AC:

390

AN:

152322

Hom.:

Cov.:

AF XY:

0.00218

AC XY:

162

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00398

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.00298

Hom.:

Bravo

AF:

0.00259

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000714

AC:

ESP6500EA

AF:

0.00415

AC:

ExAC

AF:

0.00245

AC:

297

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.00311

EpiControl

AF:

0.00344

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

GRAMD1A: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.74

CADD

Benign

3.7

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.071

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.0029

MetaRNN

Benign

0.0037

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.090

.;N;N

REVEL

Benign

0.025

Sift

Benign

0.14

.;T;T

Sift4G

Benign

0.12

T;T;T

Polyphen

0.0, 0.0010

.;B;B

Vest4

0.076

MVP

0.043

MPC

0.46

ClinPred

0.0053

GERP RS

-4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.054

gMVP

0.22

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.

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