19-17192965-T-G

Position:

• chr19-17192965-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004145.4(MYO9B):​c.3031T>G​(p.Ser1011Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,527,950 control chromosomes in the GnomAD database, including 160,502 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (23732 hom., cov: 32)
  • Exomes 𝑓: 0.43 (136770 hom.)
• Consequence: MYO9B NM_004145.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.707

Genes affected

MYO9B (HGNC:7609): (myosin IXB) This gene encodes a member of the myosin family of actin-based molecular motor heavy chain proteins. The protein represents an unconventional myosin; it should not be confused with the conventional non-muscle myosin-9 (MYH9). The protein has four IQ motifs located in the neck domain that bind calmodulin, which serves as a light chain. The protein complex has a single-headed structure and exhibits processive movement on actin filaments toward the minus-end. The protein also has rho-GTPase activity. Polymorphisms in this gene are associated with celiac disease and ulcerative colitis susceptibility. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.439414E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO9B	NM_004145.4	c.3031T>G	p.Ser1011Ala	missense_variant	21/40	ENST00000682292.1	NP_004136.2
MYO9B	NM_001130065.2	c.3031T>G	p.Ser1011Ala	missense_variant	21/40		NP_001123537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1	c.3031T>G	p.Ser1011Ala	missense_variant	21/40		NM_004145.4	ENSP00000507803.1

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81315 AN: 151912 Hom.: 23693 Cov.: 32

Gnomad AFR AF: 0.740

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.758

Gnomad SAS AF: 0.562

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.531

GnomAD3 exomes AF: 0.520 AC: 77418 AN: 148976 Hom.: 21811 AF XY: 0.509 AC XY: 40565 AN XY: 79694

Gnomad AFR exome AF: 0.754

Gnomad AMR exome AF: 0.717

Gnomad ASJ exome AF: 0.338

Gnomad EAS exome AF: 0.770

Gnomad SAS exome AF: 0.530

Gnomad FIN exome AF: 0.427

Gnomad NFE exome AF: 0.405

Gnomad OTH exome AF: 0.492

GnomAD4 exome AF: 0.434 AC: 597690 AN: 1375920 Hom.: 136770 Cov.: 46 AF XY: 0.436 AC XY: 294343 AN XY: 674462

Gnomad4 AFR exome AF: 0.759

Gnomad4 AMR exome AF: 0.705

Gnomad4 ASJ exome AF: 0.326

Gnomad4 EAS exome AF: 0.748

Gnomad4 SAS exome AF: 0.538

Gnomad4 FIN exome AF: 0.421

Gnomad4 NFE exome AF: 0.399

Gnomad4 OTH exome AF: 0.459

GnomAD4 genome AF: 0.535 AC: 81405 AN: 152030 Hom.: 23732 Cov.: 32 AF XY: 0.540 AC XY: 40086 AN XY: 74294

Gnomad4 AFR AF: 0.740

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.758

Gnomad4 SAS AF: 0.560

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.527

Alfa AF: 0.422 Hom.: 20720

Bravo AF: 0.563

TwinsUK AF: 0.402 AC: 1492

ALSPAC AF: 0.397 AC: 1529

ESP6500AA AF: 0.746 AC: 2939

ESP6500EA AF: 0.417 AC: 3377

ExAC AF: 0.403 AC: 39756

Asia WGS AF: 0.622 AC: 2161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.58
DANN	Benign	0.19
DEOGEN2	Benign	0.0071	.;T;.;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0031	N
LIST_S2	Benign	0.042	.;T;T;T
MetaRNN	Benign	0.0000024	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.7	N;.;N;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	1.7	.;.;N;.
REVEL	Benign	0.043
Sift	Benign	1.0	.;.;T;.
Sift4G	Benign	0.78	T;T;T;T
Vest4		0.035
MPC		0.27
ClinPred		0.0035	T
GERP RS		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
gMVP		0.19

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: rs1545620; hg19: chr19-17303774; COSMIC: COSV68280833; COSMIC: COSV68280833;