chr16-2209585-C-T

Variant names:

• chr16-2209585-C-T
• NM_182563.4:c.560G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.52

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]

ACMG classification

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
BRICD5	NM_182563.4	c.560G>A	p.Arg187Lys	missense_variant	Exon 5 of 6	ENST00000328540.8	NP_872369.2
MLST8	NM_022372.6	c.*708C>T		downstream_gene_variant		ENST00000569417.6	NP_071767.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRICD5	ENST00000328540.8	c.560G>A	p.Arg187Lys	missense_variant	Exon 5 of 6	1	NM_182563.4	ENSP00000332389.3
MLST8	ENST00000569417.6	c.*708C>T		downstream_gene_variant		1	NM_022372.6	ENSP00000456405.1

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

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;