10-42791727-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP3 BP4_Strong BP6_Moderate BS2

The NM_014753.4(BMS1):c.737C>T(p.Pro246Leu) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00083 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BMS1 NM_014753.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.74

Genes affected

BMS1 (HGNC:23505): (BMS1 ribosome biogenesis factor) This gene likely encodes a ribosome assembly protein. A similar protein in yeast functions in 35S-rRNA processing, which includes a series of cleavage steps critical for formation of 40S ribosomes. Related pseudogenes exist on chromosomes 2, 9, 10, 15, 16, and 22.[provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• PP3: Multiple lines of computational evidence support a deleterious effect 7: AlphaMissense, Cadd, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate, PROVEAN [when BayesDel_addAF, max_spliceai, MetaRNN, MutationTaster was below the threshold]
• BP4: Computational evidence support a benign effect (MetaRNN=0.020526499).
• BP6: Variant 10-42791727-C-T is Benign according to our data. Variant chr10-42791727-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3043996.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 310 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BMS1	NM_014753.4	c.737C>T	p.Pro246Leu	missense_variant	6/23	ENST00000374518.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BMS1	ENST00000374518.6	c.737C>T	p.Pro246Leu	missense_variant	6/23	1	NM_014753.4	P1

Frequencies

GnomAD3 genomes AF: 0.00205 AC: 310 AN: 151370 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00422

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00250

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00921

Gnomad SAS AF: 0.00293

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00185 AC: 460 AN: 248770 Hom.: 0 AF XY: 0.00166 AC XY: 223 AN XY: 134564

Gnomad AFR exome AF: 0.00299

Gnomad AMR exome AF: 0.00502

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00637

Gnomad SAS exome AF: 0.00289

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000318

Gnomad OTH exome AF: 0.000823

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000830 AC: 1210 AN: 1457270 Hom.: 0 Cov.: 30 AF XY: 0.000891 AC XY: 646 AN XY: 724914

Gnomad4 AFR exome AF: 0.00284

Gnomad4 AMR exome AF: 0.00626

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00646

Gnomad4 SAS exome AF: 0.00304

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000212

Gnomad4 OTH exome AF: 0.00148

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00205 AC: 310 AN: 151486 Hom.: 0 Cov.: 32 AF XY: 0.00206 AC XY: 153 AN XY: 74092

Gnomad4 AFR AF: 0.00424

Gnomad4 AMR AF: 0.00250

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00904

Gnomad4 SAS AF: 0.00293

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00177 Hom.: 0

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00436 AC: 530

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

BMS1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 12, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.70
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Uncertain	-0.070
Cadd	Pathogenic	30
Dann	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
MetaRNN	Benign	0.021	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Pathogenic	3.0	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-8.9	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.81
MVP		0.64
MPC		0.50
ClinPred		0.077	T
GERP RS		5.5
Varity_R		0.72
gMVP		0.73

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

LitVar

Other links and lift over

dbSNP: rs116522292; hg19: chr10-43287175; COSMIC: COSV65734944;