NM_001080467.3:c.*308C>T

Variant names:

• chr18-49826163-G-A
• rs555879
• NM_001080467.3:c.*308C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001080467.3(MYO5B):​c.*308C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.54 in 366,126 control chromosomes in the GnomAD database, including 53,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (22089 hom., cov: 33)
  • Exomes 𝑓: 0.54 (31719 hom.)
• Consequence: MYO5B NM_001080467.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.246
• Publications: 9 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 18-49826163-G-A is Benign according to our data. Variant chr18-49826163-G-A is described in ClinVar as Benign. ClinVar VariationId is 326990.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.601 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	NM_001080467.3	MANE Select	c.*308C>T		3_prime_UTR	Exon 40 of 40	NP_001073936.1
	SNHG22	NR_117096.1		n.40+12101G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO5B	ENST00000285039.12	TSL:1 MANE Select	c.*308C>T		3_prime_UTR	Exon 40 of 40	ENSP00000285039.6
	ENSG00000266997	ENST00000590532.2	TSL:5	n.*35+273C>T		intron	N/A	ENSP00000467396.2
	MYO5B	ENST00000697218.1		n.2759C>T		non_coding_transcript_exon	Exon 17 of 17

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81647 AN: 151884 Hom.: 22074 Cov.: 33

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.611

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.577

GnomAD4 exome AF: 0.541 AC: 115827 AN: 214124 Hom.: 31719 Cov.: 2 AF XY: 0.542 AC XY: 62313 AN XY: 114920

African (AFR) AF: 0.535 AC: 3460 AN: 6470

American (AMR) AF: 0.630 AC: 5869 AN: 9320

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 3638 AN: 5866

East Asian (EAS) AF: 0.453 AC: 4997 AN: 11034

South Asian (SAS) AF: 0.550 AC: 18813 AN: 34224

European-Finnish (FIN) AF: 0.456 AC: 4348 AN: 9530

Middle Eastern (MID) AF: 0.572 AC: 484 AN: 846

European-Non Finnish (NFE) AF: 0.543 AC: 68132 AN: 125492

Other (OTH) AF: 0.537 AC: 6086 AN: 11342

GnomAD4 genome AF: 0.538 AC: 81711 AN: 152002 Hom.: 22089 Cov.: 33 AF XY: 0.538 AC XY: 39936 AN XY: 74276

African (AFR) AF: 0.526 AC: 21784 AN: 41440

American (AMR) AF: 0.611 AC: 9352 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2154 AN: 3472

East Asian (EAS) AF: 0.414 AC: 2141 AN: 5174

South Asian (SAS) AF: 0.542 AC: 2610 AN: 4814

European-Finnish (FIN) AF: 0.463 AC: 4879 AN: 10530

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.541 AC: 36788 AN: 67968

Other (OTH) AF: 0.573 AC: 1207 AN: 2106

Alfa AF: 0.538 Hom.: 2800

Bravo AF: 0.549

Asia WGS AF: 0.505 AC: 1755 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital microvillous atrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.54
PhyloP100		-0.25
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: rs555879; hg19: chr18-47352533;