16-2209405-C-T

Variant summary

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

The NM_182563.4(BRICD5):​c.644G>A​(p.Ser215Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,613,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S215C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

BRICD5
NM_182563.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.62
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]
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]

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=0.1358279).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRICD5NM_182563.4 linkc.644G>A p.Ser215Asn missense_variant Exon 6 of 6 ENST00000328540.8 NP_872369.2 Q6PL45-2
MLST8NM_022372.6 linkc.*528C>T 3_prime_UTR_variant Exon 9 of 9 ENST00000569417.6 NP_071767.3 Q9BVC4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRICD5ENST00000328540.8 linkc.644G>A p.Ser215Asn missense_variant Exon 6 of 6 1 NM_182563.4 ENSP00000332389.3 Q6PL45-2
MLST8ENST00000569417.6 linkc.*528C>T 3_prime_UTR_variant Exon 9 of 9 1 NM_022372.6 ENSP00000456405.1 Q9BVC4-1

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152198
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000438
AC:
11
AN:
251042
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135800
show subpopulations
Gnomad AFR exome
AF:
0.000370
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000219
AC:
32
AN:
1461502
Hom.:
0
Cov.:
33
AF XY:
0.0000206
AC XY:
15
AN XY:
727070
show subpopulations
Gnomad4 AFR exome
AF:
0.000478
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000919
AC:
14
AN:
152316
Hom.:
0
Cov.:
34
AF XY:
0.0000940
AC XY:
7
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000132
Hom.:
0
Bravo
AF:
0.000102
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000824
AC:
10

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.644G>A (p.S215N) alteration is located in exon 6 (coding exon 6) of the BRICD5 gene. This alteration results from a G to A substitution at nucleotide position 644, causing the serine (S) at amino acid position 215 to be replaced by an asparagine (N). 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
0.32
BayesDel_addAF
Benign
-0.43
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.082
.;T
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.018
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.61
T;T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.14
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
.;L
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-1.8
N;N
REVEL
Benign
0.058
Sift
Benign
0.083
T;T
Sift4G
Benign
0.098
T;T
Polyphen
0.23
B;B
Vest4
0.35
MVP
0.31
MPC
0.0035
ClinPred
0.055
T
GERP RS
1.9
Varity_R
0.21
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs200527596; hg19: chr16-2259406; API