chr22-25761136-G-T

Variant names:

• chr22-25761136-G-T
• rs1568977389
• NM_032608.7:c.39+5G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032608.7(MYO18B):​c.39+5G>T variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00000137 in 1,460,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MYO18B NM_032608.7 splice_region, intron
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.75

Genes affected

MYO18B (HGNC:18150): (myosin XVIIIB) The protein encoded by this gene may regulate muscle-specific genes when in the nucleus and may influence intracellular trafficking when in the cytoplasm. The encoded protein functions as a homodimer and may interact with F actin. Mutations in this gene are associated with lung cancer. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO18B	NM_032608.7	c.39+5G>T		splice_region_variant, intron_variant	Intron 2 of 43	ENST00000335473.12	NP_115997.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO18B	ENST00000335473.12	c.39+5G>T		splice_region_variant, intron_variant	Intron 2 of 43	1	NM_032608.7	ENSP00000334563.8
MYO18B	ENST00000407587.6	c.39+5G>T		splice_region_variant, intron_variant	Intron 2 of 43	1		ENSP00000386096.2
MYO18B	ENST00000536101.5	c.39+5G>T		splice_region_variant, intron_variant	Intron 2 of 42	1		ENSP00000441229.1
MYO18B	ENST00000539302.5	n.39+5G>T		splice_region_variant, intron_variant	Intron 1 of 41	1		ENSP00000437587.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248500 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134832

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000556

Gnomad SAS 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: 0.00000137 AC: 2 AN: 1460884 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726748

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Klippel-Feil anomaly-myopathy-facial dysmorphism syndrome Uncertain:1

-

Juno Genomics, Hangzhou Juno Genomics, Inc

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PM2_Supporting+PM3 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	20
DANN	Benign	0.97

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1568977389; hg19: chr22-26157103;