chr19-17192965-T-G

Variant names:

• chr19-17192965-T-G
• rs1545620
• NM_004145.4:c.3031T>G

Variant summary

Our verdict is Benign. The variant received -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. 15/20 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
• Publications: 66 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MYO9B	NM_004145.4	c.3031T>G	p.Ser1011Ala	missense_variant	Exon 21 of 40	ENST00000682292.1	NP_004136.2
MYO9B	NM_001130065.2	c.3031T>G	p.Ser1011Ala	missense_variant	Exon 21 of 40		NP_001123537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO9B	ENST00000682292.1	c.3031T>G	p.Ser1011Ala	missense_variant	Exon 21 of 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

GnomAD2 exomes AF: 0.520 AC: 77418 AN: 148976 AF XY: 0.509

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 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

African (AFR) AF: 0.759 AC: 23746 AN: 31282

American (AMR) AF: 0.705 AC: 24564 AN: 34834

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 8049 AN: 24666

East Asian (EAS) AF: 0.748 AC: 26363 AN: 35228

South Asian (SAS) AF: 0.538 AC: 42226 AN: 78416

European-Finnish (FIN) AF: 0.421 AC: 19220 AN: 45604

Middle Eastern (MID) AF: 0.512 AC: 2867 AN: 5598

European-Non Finnish (NFE) AF: 0.399 AC: 424503 AN: 1063370

Other (OTH) AF: 0.459 AC: 26152 AN: 56922

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

African (AFR) AF: 0.740 AC: 30732 AN: 41502

American (AMR) AF: 0.627 AC: 9586 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1156 AN: 3472

East Asian (EAS) AF: 0.758 AC: 3918 AN: 5168

South Asian (SAS) AF: 0.560 AC: 2701 AN: 4826

European-Finnish (FIN) AF: 0.442 AC: 4660 AN: 10540

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.399 AC: 27072 AN: 67924

Other (OTH) AF: 0.527 AC: 1114 AN: 2112

Alfa AF: 0.437 Hom.: 51595

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;.
PhyloP100		0.71
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
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: rs1545620; hg19: chr19-17303774; COSMIC: COSV68280833; COSMIC: COSV68280833;