rs149422405

Variant names:

• chr16-15586774-C-T
• rs149422405
• NM_033201.3:c.560C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-15586774-C-T
• chr16-15586774-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_033201.3(BMERB1):​c.560C>T​(p.Thr187Met) variant causes a missense change. The variant allele was found at a frequency of 0.000737 in 1,612,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00077 (0 hom.)
• Consequence: BMERB1 NM_033201.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.13
• Publications: 1 publications found

Genes affected

BMERB1 (HGNC:19213): (bMERB domain containing 1) Predicted to act upstream of or within negative regulation of cell motility involved in cerebral cortex radial glia guided migration and negative regulation of microtubule depolymerization. Predicted to be located in microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

MPV17L-BMERB1 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13430798).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033201.3. 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
	BMERB1	NM_033201.3	MANE Select	c.560C>T	p.Thr187Met	missense	Exon 6 of 6	NP_149978.1	Q96MC5-1
	MPV17L-BMERB1	NM_001414674.1		c.764C>T	p.Thr255Met	missense	Exon 6 of 6	NP_001401603.1
	BMERB1	NM_001142469.2		c.509C>T	p.Thr170Met	missense	Exon 6 of 6	NP_001135941.1	Q96MC5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMERB1	ENST00000300006.9	TSL:1 MANE Select	c.560C>T	p.Thr187Met	missense	Exon 6 of 6	ENSP00000300006.4	Q96MC5-1
	BMERB1	ENST00000452191.6	TSL:1	c.509C>T	p.Thr170Met	missense	Exon 6 of 6	ENSP00000408976.2	Q96MC5-2
	BMERB1	ENST00000869050.1		c.554C>T	p.Thr185Met	missense	Exon 6 of 6	ENSP00000539109.1

Frequencies

GnomAD3 genomes AF: 0.000460 AC: 70 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000853

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000303 AC: 74 AN: 244184 AF XY: 0.000295

Gnomad AFR exome AF: 0.0000640

Gnomad AMR exome AF: 0.0000587

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000191

Gnomad NFE exome AF: 0.000592

Gnomad OTH exome AF: 0.000337

GnomAD4 exome AF: 0.000766 AC: 1118 AN: 1460344 Hom.: 0 Cov.: 31 AF XY: 0.000749 AC XY: 544 AN XY: 726274

African (AFR) AF: 0.000149 AC: 5 AN: 33476

American (AMR) AF: 0.0000674 AC: 3 AN: 44500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26040

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39634

South Asian (SAS) AF: 0.00 AC: 0 AN: 85730

European-Finnish (FIN) AF: 0.000206 AC: 11 AN: 53284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000971 AC: 1079 AN: 1111594

Other (OTH) AF: 0.000315 AC: 19 AN: 60320

GnomAD4 genome AF: 0.000460 AC: 70 AN: 152222 Hom.: 0 Cov.: 32 AF XY: 0.000430 AC XY: 32 AN XY: 74366

African (AFR) AF: 0.000193 AC: 8 AN: 41458

American (AMR) AF: 0.0000654 AC: 1 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000853 AC: 58 AN: 68034

Other (OTH) AF: 0.000955 AC: 2 AN: 2094

Alfa AF: 0.000507 Hom.: 0

Bravo AF: 0.000427

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00130 AC: 5

ESP6500AA AF: 0.000228 AC: 1

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000222 AC: 27

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	0.17
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	29
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.099	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.28	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		7.1
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.27
MVP		0.24
MPC		0.49
ClinPred		0.35	T
GERP RS		4.9
Varity_R		0.24
gMVP		0.68
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

dbSNP: rs149422405; hg19: chr16-15680631; COSMIC: COSV55513145; COSMIC: COSV55513145;