10-42787242-G-A

Variant names:

• chr10-42787242-G-A
• rs565731481
• NM_014753.4:c.442G>A

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_014753.4(BMS1):​c.442G>A​(p.Asp148Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. D148Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BMS1 NM_014753.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.65
• Publications: 0 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.956

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.442G>A	p.Asp148Asn	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.442G>A	p.Asp148Asn	missense	Exon 4 of 23	ENSP00000363642.4	Q14692
	BMS1	ENST00000877424.1		c.442G>A	p.Asp148Asn	missense	Exon 4 of 24	ENSP00000547483.1
	BMS1	ENST00000966891.1		c.442G>A	p.Asp148Asn	missense	Exon 4 of 23	ENSP00000636950.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 15

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
PhyloP100		9.7
Varity_R		0.81
gMVP		0.92
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs565731481; hg19: chr10-43282690;