18-49823189-C-T

Variant names:

• chr18-49823189-C-T
• rs371042751
• NM_001080467.3:c.*3282G>A

Variant summary

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

The NM_001080467.3(MYO5B):​c.*3282G>A 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 0.37 (0 hom., cov: 38)
  • Failed GnomAD Quality Control
• Consequence: MYO5B NM_001080467.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.261
• Publications: 2 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=-0.86).

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.*3282G>A		3_prime_UTR	Exon 40 of 40	NP_001073936.1	Q9ULV0-1
	SNHG22	NR_117096.1		n.40+9127C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.*3282G>A		3_prime_UTR	Exon 40 of 40	ENSP00000285039.6	Q9ULV0-1
	ENSG00000266997	ENST00000590532.2	TSL:5	n.*35+3247G>A		intron	N/A	ENSP00000467396.2	K7EPI3
	MYO5B	ENST00000697219.1		c.*3282G>A		3_prime_UTR	Exon 38 of 38	ENSP00000513188.1	A0A8V8TM52

Frequencies

GnomAD3 genomes AF: 0.374 AC: 20896 AN: 55866 Hom.: 0 Cov.: 38

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.460

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.367

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.374 AC: 20921 AN: 55922 Hom.: 0 Cov.: 38 AF XY: 0.365 AC XY: 10109 AN XY: 27666

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

African (AFR) AF: 0.369 AC: 5737 AN: 15540

American (AMR) AF: 0.371 AC: 2175 AN: 5870

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 420 AN: 1136

East Asian (EAS) AF: 0.382 AC: 733 AN: 1920

South Asian (SAS) AF: 0.347 AC: 627 AN: 1808

European-Finnish (FIN) AF: 0.373 AC: 1654 AN: 4440

Middle Eastern (MID) AF: 0.466 AC: 54 AN: 116

European-Non Finnish (NFE) AF: 0.380 AC: 9119 AN: 24004

Other (OTH) AF: 0.368 AC: 283 AN: 768

⚠️ 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: 0.427 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	-0.86
CADD	Benign	0.99
DANN	Benign	0.53
PhyloP100		-0.26
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: rs371042751; hg19: chr18-47349559;