chr10-42787177-G-T

Variant names:

• chr10-42787177-G-T
• rs755400315
• NM_014753.4:c.377G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014753.4(BMS1):​c.377G>T​(p.Arg126Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000937 in 1,067,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. R126C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 9.4e-7 (0 hom.)
• Consequence: BMS1 NM_014753.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.65
• Publications: 1 publications found

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]

BMS1 Gene-Disease associations (from GenCC):

• aplasia cutis congenita

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.816

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014753.4. 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
	BMS1	NM_014753.4	MANE Select	c.377G>T	p.Arg126Leu	missense	Exon 4 of 23	NP_055568.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BMS1	ENST00000374518.6	TSL:1 MANE Select	c.377G>T	p.Arg126Leu	missense	Exon 4 of 23	ENSP00000363642.4	Q14692
	BMS1	ENST00000877424.1		c.377G>T	p.Arg126Leu	missense	Exon 4 of 24	ENSP00000547483.1
	BMS1	ENST00000966891.1		c.377G>T	p.Arg126Leu	missense	Exon 4 of 23	ENSP00000636950.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.37e-7 AC: 1 AN: 1067736 Hom.: 0 Cov.: 15 AF XY: 0.00000182 AC XY: 1 AN XY: 548684

African (AFR) AF: 0.00 AC: 0 AN: 25804

American (AMR) AF: 0.00 AC: 0 AN: 43470

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23688

East Asian (EAS) AF: 0.0000264 AC: 1 AN: 37908

South Asian (SAS) AF: 0.00 AC: 0 AN: 77578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3372

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 770686

Other (OTH) AF: 0.00 AC: 0 AN: 47532

GnomAD4 genome Cov.: 32

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	Pathogenic	0.76
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		9.7
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.033	D
Polyphen		0.22	B
Vest4		0.90
MutPred		0.64		Loss of MoRF binding (P = 0.0445)
MVP		0.88
MPC		2.5
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.76
gMVP		0.87
Mutation Taster		=28/72	disease causing

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: rs755400315; hg19: chr10-43282625;