rs1017228

Variant names:

• chr16-22052396-T-C
• rs1017228
• NM_001164579.2:c.107-23091T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001164579.2(MOSMO):​c.107-23091T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,106 control chromosomes in the GnomAD database, including 18,901 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (18901 hom., cov: 32)
• Consequence: MOSMO NM_001164579.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.48
• Publications: 6 publications found

Genes affected

MOSMO (HGNC:27087): (modulator of smoothened) Predicted to be involved in negative regulation of smoothened signaling pathway; regulation of neuron differentiation; and regulation of protein stability. Predicted to be located in plasma membrane. Predicted to be active in Golgi apparatus and ciliary membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164579.2. 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
	MOSMO	NM_001164579.2	MANE Select	c.107-23091T>C		intron	N/A	NP_001158051.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MOSMO	ENST00000542527.7	TSL:5 MANE Select	c.107-23091T>C		intron	N/A	ENSP00000454926.1
	MOSMO	ENST00000567004.1	TSL:1	c.53-23091T>C		intron	N/A	ENSP00000456506.1
	MOSMO	ENST00000331057.8	TSL:1	n.107-11942T>C		intron	N/A	ENSP00000454543.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65820 AN: 151988 Hom.: 18859 Cov.: 32

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.701

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.408

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.433 AC: 65915 AN: 152106 Hom.: 18901 Cov.: 32 AF XY: 0.437 AC XY: 32501 AN XY: 74372

African (AFR) AF: 0.789 AC: 32755 AN: 41496

American (AMR) AF: 0.361 AC: 5519 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1202 AN: 3464

East Asian (EAS) AF: 0.701 AC: 3620 AN: 5164

South Asian (SAS) AF: 0.611 AC: 2948 AN: 4824

European-Finnish (FIN) AF: 0.210 AC: 2224 AN: 10580

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16539 AN: 67976

Other (OTH) AF: 0.414 AC: 875 AN: 2112

Alfa AF: 0.301 Hom.: 13824

Bravo AF: 0.451

Asia WGS AF: 0.663 AC: 2301 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.53
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs1017228; hg19: chr16-22063717;