chr10-42787242-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PP3_Moderate BS2

The NM_014753.4(BMS1):​c.442G>C​(p.Asp148His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000185 in 1,245,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. D148Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• Consequence: BMS1 NM_014753.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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_benign. The variant received -2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.892
• BS2: High AC in GnomAd4 at 14 AD gene.

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>C	p.Asp148His	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>C	p.Asp148His	missense	Exon 4 of 23	ENSP00000363642.4	Q14692
	BMS1	ENST00000877424.1		c.442G>C	p.Asp148His	missense	Exon 4 of 24	ENSP00000547483.1
	BMS1	ENST00000966891.1		c.442G>C	p.Asp148His	missense	Exon 4 of 23	ENSP00000636950.1

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152138 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.0000199 AC: 4 AN: 200548 AF XY: 0.00000905

Gnomad AFR exome AF: 0.000168

Gnomad AMR exome AF: 0.0000665

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000823 AC: 9 AN: 1093218 Hom.: 0 Cov.: 15 AF XY: 0.00000358 AC XY: 2 AN XY: 559122

African (AFR) AF: 0.0000756 AC: 2 AN: 26464

American (AMR) AF: 0.0000487 AC: 2 AN: 41026

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23696

East Asian (EAS) AF: 0.00 AC: 0 AN: 37760

South Asian (SAS) AF: 0.00 AC: 0 AN: 77184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36968

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3484

European-Non Finnish (NFE) AF: 0.00000501 AC: 4 AN: 798140

Other (OTH) AF: 0.0000206 AC: 1 AN: 48496

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152256 Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6 AN XY: 74466

African (AFR) AF: 0.000265 AC: 11 AN: 41556

American (AMR) AF: 0.0000654 AC: 1 AN: 15298

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000144

ExAC AF: 0.0000264 AC: 3

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	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	32
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.80
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Uncertain	0.087	D
MetaRNN	Pathogenic	0.89	D
MetaSVM	Benign	-0.31	T
MutationAssessor	Pathogenic	4.4	H
PhyloP100		9.7
PrimateAI	Pathogenic	0.87	D
PROVEAN	Pathogenic	-6.8	D
REVEL	Pathogenic	0.69
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.91
MutPred		0.83		Gain of helix (P = 0.0854)
MVP		0.75
MPC		4.0
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.88
gMVP		0.96
Mutation Taster		=23/77	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: rs565731481; hg19: chr10-43282690;