rs11611277

Positions:

• chr12-109388829-C-A
• chr12-109388829-C-T

Variant summary

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

The NM_001101421.4(MYO1H):​c.159C>A​(p.Ser53Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 1,610,846 control chromosomes in the GnomAD database, including 37,913 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 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 0.17 (2858 hom., cov: 32)
  • Exomes 𝑓: 0.21 (35055 hom.)
• Consequence: MYO1H NM_001101421.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

Genes affected

MYO1H (HGNC:13879): (myosin IH) Predicted to enable actin filament binding activity and microfilament motor activity. Predicted to be involved in actin filament organization and vesicle transport along actin filament. Predicted to be part of myosin complex. Predicted to be active in several cellular components, including actin cytoskeleton; microvillus; and vesicle. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00410828).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1H	NM_001101421.4	c.159C>A	p.Ser53Arg	missense_variant	2/32	ENST00000310903.10	NP_001094891.4
MYO1H	XM_011538223.3	c.111C>A	p.Ser37Arg	missense_variant	3/34		XP_011536525.1
MYO1H	XM_047428738.1	c.111C>A	p.Ser37Arg	missense_variant	1/31		XP_047284694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1H	ENST00000310903.10	c.159C>A	p.Ser53Arg	missense_variant	2/32	5	NM_001101421.4	ENSP00000439182.2

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25676 AN: 151982 Hom.: 2860 Cov.: 32

Gnomad AFR AF: 0.0402

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.191

GnomAD3 exomes AF: 0.212 AC: 52401 AN: 247576 Hom.: 6563 AF XY: 0.208 AC XY: 27991 AN XY: 134348

Gnomad AFR exome AF: 0.0353

Gnomad AMR exome AF: 0.375

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.139

Gnomad SAS exome AF: 0.165

Gnomad FIN exome AF: 0.151

Gnomad NFE exome AF: 0.223

Gnomad OTH exome AF: 0.213

GnomAD4 exome AF: 0.213 AC: 310885 AN: 1458744 Hom.: 35055 Cov.: 32 AF XY: 0.212 AC XY: 153666 AN XY: 725496

Gnomad4 AFR exome AF: 0.0319

Gnomad4 AMR exome AF: 0.370

Gnomad4 ASJ exome AF: 0.203

Gnomad4 EAS exome AF: 0.168

Gnomad4 SAS exome AF: 0.165

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.195

GnomAD4 genome AF: 0.169 AC: 25666 AN: 152102 Hom.: 2858 Cov.: 32 AF XY: 0.167 AC XY: 12439 AN XY: 74352

Gnomad4 AFR AF: 0.0401

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.190

Alfa AF: 0.205 Hom.: 5050

Bravo AF: 0.179

TwinsUK AF: 0.222 AC: 825

ALSPAC AF: 0.223 AC: 860

ESP6500AA AF: 0.0427 AC: 176

ESP6500EA AF: 0.211 AC: 1775

ExAC AF: 0.202 AC: 24400

EpiCase AF: 0.231

EpiControl AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	13
DANN	Benign	0.17
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.72	T;T
MetaRNN	Benign	0.0041	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.080	.;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.4	.;N
REVEL	Benign	0.20
Sift	Benign	1.0	.;T
Sift4G	Benign	0.97	T;T
Vest4		0.061
MutPred		0.42		.;Gain of catalytic residue at N39 (P = 0.0012);
MPC		0.092
ClinPred		0.0019	T
GERP RS		0.46
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11611277; hg19: chr12-109826634; COSMIC: COSV60450855;