Genetic Variant BRICD5:p.Gly178Glu (chr16-2209612-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

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

The NM_182563.4(BRICD5):c.533G>A(p.Gly178Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,946 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: 34)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

BRICD5
NM_182563.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53

Variant links:

Genes affected

BRICD5 (HGNC:28309): (BRICHOS domain containing 5) Predicted to be involved in regulation of cell population proliferation. Predicted to be integral component of membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

BRICD5 links:

MLST8 (HGNC:24825): (MTOR associated protein, LST8 homolog) Enables protein serine/threonine kinase activator activity. Involved in TORC1 signaling; positive regulation of TOR signaling; and regulation of actin cytoskeleton organization. Part of TORC1 complex and TORC2 complex. [provided by Alliance of Genome Resources, Apr 2022]

MLST8 links:

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=0.41506898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRICD5	NM_182563.4 link	c.533G>A	p.Gly178Glu	missense_variant	Exon 5 of 6	ENST00000328540.8	NP_872369.2	Q6PL45-2
MLST8	NM_022372.6 link	c.*735C>T		downstream_gene_variant		ENST00000569417.6	NP_071767.3	Q9BVC4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRICD5	ENST00000328540.8 link	c.533G>A	p.Gly178Glu	missense_variant	Exon 5 of 6	1	NM_182563.4	ENSP00000332389.3		Q6PL45-2
MLST8	ENST00000569417.6 link	c.*735C>T		downstream_gene_variant		1	NM_022372.6	ENSP00000456405.1		Q9BVC4-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

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

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460734

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726742

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

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:

0.00000630

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74360

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

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 19, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.533G>A (p.G178E) alteration is located in exon 5 (coding exon 5) of the BRICD5 gene. This alteration results from a G to A substitution at nucleotide position 533, causing the glycine (G) at amino acid position 178 to be replaced by a glutamic acid (E). 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

Pathogenic

0.58

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.76

T;T

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.42

T;T

MetaSVM

Uncertain

0.51

MutationAssessor

Uncertain

2.6

M;M

PrimateAI

Uncertain

0.48

PROVEAN

Pathogenic

-5.1

D;D

REVEL

Uncertain

0.46

Sift

Benign

0.30

T;T

Sift4G

Benign

0.39

T;T

Polyphen

1.0

D;D

Vest4

0.29

MutPred

0.46

Loss of MoRF binding (P = 0.0662);Loss of MoRF binding (P = 0.0662);

MVP

0.50

MPC

0.0071

ClinPred

0.97

GERP RS

5.0

Varity_R

0.49

gMVP

0.73

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