16-2209405-C-G

Variant names:

• chr16-2209405-C-G
• rs200527596
• NM_182563.4:c.644G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_182563.4(BRICD5):​c.644G>C​(p.Ser215Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 34)
• Consequence: BRICD5 NM_182563.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182563.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRICD5	NM_182563.4	MANE Select	c.644G>C	p.Ser215Thr	missense	Exon 6 of 6	NP_872369.2	Q6PL45-2
	MLST8	NM_022372.6	MANE Select	c.*528C>G		3_prime_UTR	Exon 9 of 9	NP_071767.3
	MLST8	NM_001352057.2		c.*528C>G		3_prime_UTR	Exon 9 of 9	NP_001338986.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRICD5	ENST00000328540.8	TSL:1 MANE Select	c.644G>C	p.Ser215Thr	missense	Exon 6 of 6	ENSP00000332389.3	Q6PL45-2
	MLST8	ENST00000569417.6	TSL:1 MANE Select	c.*528C>G		3_prime_UTR	Exon 9 of 9	ENSP00000456405.1	Q9BVC4-1
	MLST8	ENST00000301724.14	TSL:1	c.*670C>G		3_prime_UTR	Exon 8 of 8	ENSP00000301724.10	A0A0A0MR05

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.6
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.15
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.017	D
Polyphen		0.99	D
Vest4		0.59
MutPred		0.34		Loss of glycosylation at S247 (P = 0.1231)
MVP		0.34
MPC		0.0084
ClinPred		0.97	D
GERP RS		1.9
Varity_R		0.43
gMVP		0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs200527596; hg19: chr16-2259406;