chr18-49823198-C-G

Variant names:

• chr18-49823198-C-G
• rs9947739
• NM_001080467.3:c.*3273G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001080467.3(MYO5B):​c.*3273G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.33 (0 hom., cov: 38)
  • Exomes 𝑓: 0.50 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYO5B NM_001080467.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.479
• Publications: 1 publications found

Genes affected

MYO5B (HGNC:7603): (myosin VB) The protein encoded by this gene, together with other proteins, may be involved in plasma membrane recycling. Mutations in this gene are associated with microvillous inclusion disease. [provided by RefSeq, Sep 2009]

ENSG00000266997 (HGNC:):

SNHG22 (HGNC:50285): (small nucleolar RNA host gene 22)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001080467.3. 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
	MYO5B	NM_001080467.3	MANE Select	c.*3273G>C		3_prime_UTR	Exon 40 of 40	NP_001073936.1	Q9ULV0-1
	SNHG22	NR_117096.1		n.40+9136C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.*3273G>C		3_prime_UTR	Exon 40 of 40	ENSP00000285039.6	Q9ULV0-1
	ENSG00000266997	ENST00000590532.2	TSL:5	n.*35+3238G>C		intron	N/A	ENSP00000467396.2	K7EPI3
	MYO5B	ENST00000697219.1		c.*3273G>C		3_prime_UTR	Exon 38 of 38	ENSP00000513188.1	A0A8V8TM52

Frequencies

GnomAD3 genomes AF: 0.329 AC: 19008 AN: 57802 Hom.: 0 Cov.: 38

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.330

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.329 AC: 19027 AN: 57850 Hom.: 0 Cov.: 38 AF XY: 0.319 AC XY: 9194 AN XY: 28810

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.280 AC: 5012 AN: 17878

American (AMR) AF: 0.346 AC: 2031 AN: 5868

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 393 AN: 1130

East Asian (EAS) AF: 0.364 AC: 683 AN: 1876

South Asian (SAS) AF: 0.218 AC: 513 AN: 2358

European-Finnish (FIN) AF: 0.359 AC: 1546 AN: 4312

Middle Eastern (MID) AF: 0.414 AC: 48 AN: 116

European-Non Finnish (NFE) AF: 0.363 AC: 8435 AN: 23226

Other (OTH) AF: 0.332 AC: 261 AN: 786

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.101 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Congenital microvillous atrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.42
PhyloP100		-0.48
Mutation Taster		=100/0	polymorphism

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: rs9947739; hg19: chr18-47349568;