chr16-2209585-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_182563.4(BRICD5):​c.560G>A​(p.Arg187Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 34)

Consequence

BRICD5
NM_182563.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.52
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.039227813).
BP6
Variant 16-2209585-C-T is Benign according to our data. Variant chr16-2209585-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2459693.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRICD5NM_182563.4 linkc.560G>A p.Arg187Lys missense_variant Exon 5 of 6 ENST00000328540.8 NP_872369.2 Q6PL45-2
MLST8NM_022372.6 linkc.*708C>T downstream_gene_variant ENST00000569417.6 NP_071767.3 Q9BVC4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRICD5ENST00000328540.8 linkc.560G>A p.Arg187Lys missense_variant Exon 5 of 6 1 NM_182563.4 ENSP00000332389.3 Q6PL45-2
MLST8ENST00000569417.6 linkc.*708C>T downstream_gene_variant 1 NM_022372.6 ENSP00000456405.1 Q9BVC4-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Feb 14, 2023
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
8.3
DANN
Benign
0.71
DEOGEN2
Benign
0.0024
.;T
Eigen
Benign
-1.0
Eigen_PC
Benign
-0.99
FATHMM_MKL
Benign
0.0075
N
LIST_S2
Benign
0.47
T;T
M_CAP
Benign
0.0078
T
MetaRNN
Benign
0.039
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-1.2
N;N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
0.060
N;N
REVEL
Benign
0.12
Sift
Benign
1.0
T;T
Sift4G
Benign
0.92
T;T
Polyphen
0.0
B;B
Vest4
0.13
MutPred
0.32
Gain of solvent accessibility (P = 0.0246);Gain of solvent accessibility (P = 0.0246);
MVP
0.37
MPC
0.0026
ClinPred
0.024
T
GERP RS
3.7
Varity_R
0.060
gMVP
0.25

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.

Other links and lift over

hg19: chr16-2259586; API