rs1017228

Positions:

• chr16-22052396-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MOSMO	NM_001164579.2	c.107-23091T>C		intron_variant		ENST00000542527.7
MOSMO	XM_047434583.1	c.81-23091T>C		intron_variant
MOSMO	XR_007064906.1	n.298-23091T>C		intron_variant, non_coding_transcript_variant
MOSMO	XR_007064907.1	n.298-23091T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MOSMO	ENST00000542527.7	c.107-23091T>C		intron_variant		5	NM_001164579.2	P1

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

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.701

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.243

Gnomad4 OTH AF: 0.414

Alfa AF: 0.285 Hom.: 9552

Bravo AF: 0.451

Asia WGS AF: 0.663 AC: 2301 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.53

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: rs1017228; hg19: chr16-22063717;