16-2209405-C-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_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. 14/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.1358279).

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>A	p.Ser215Asn	missense	Exon 6 of 6	NP_872369.2	Q6PL45-2
	MLST8	NM_022372.6	MANE Select	c.*528C>T		3_prime_UTR	Exon 9 of 9	NP_071767.3
	MLST8	NM_001352057.2		c.*528C>T		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>A	p.Ser215Asn	missense	Exon 6 of 6	ENSP00000332389.3	Q6PL45-2
	MLST8	ENST00000569417.6	TSL:1 MANE Select	c.*528C>T		3_prime_UTR	Exon 9 of 9	ENSP00000456405.1	Q9BVC4-1
	MLST8	ENST00000301724.14	TSL:1	c.*670C>T		3_prime_UTR	Exon 8 of 8	ENSP00000301724.10	A0A0A0MR05

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152198 Hom.: 0 Cov.: 34

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

GnomAD2 exomes AF: 0.0000438 AC: 11 AN: 251042 AF XY: 0.0000368

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 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

African (AFR) AF: 0.000478 AC: 16 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53106

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111962

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome AF: 0.0000919 AC: 14 AN: 152316 Hom.: 0 Cov.: 34 AF XY: 0.0000940 AC XY: 7 AN XY: 74464

African (AFR) AF: 0.000313 AC: 13 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2116

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

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		1.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.058
Sift	Benign	0.083	T
Sift4G	Benign	0.098	T
Polyphen		0.23	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
Mutation Taster		=60/40	polymorphism

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

Other links and lift over

dbSNP: rs200527596; hg19: chr16-2259406;