rs11611277

Variant names:

• chr12-109388829-C-A
• rs11611277
• NM_001101421.4:c.159C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. 16/20 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 0.17 (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
• Publications: 29 publications found

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]

MYO1H Gene-Disease associations (from GenCC):

• congenital central hypoventilation syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• central hypoventilation syndrome, congenital, 2, and autonomic dysfunction

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001101421.4. 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
	MYO1H	NM_001101421.4	MANE Select	c.159C>A	p.Ser53Arg	missense	Exon 2 of 32	NP_001094891.4	A0A140TA25

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1H	ENST00000310903.10	TSL:5 MANE Select	c.159C>A	p.Ser53Arg	missense	Exon 2 of 32	ENSP00000439182.2	A0A140TA25

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

GnomAD2 exomes AF: 0.212 AC: 52401 AN: 247576 AF XY: 0.208

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 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

African (AFR) AF: 0.0319 AC: 1066 AN: 33412

American (AMR) AF: 0.370 AC: 16429 AN: 44344

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 5293 AN: 26046

East Asian (EAS) AF: 0.168 AC: 6658 AN: 39672

South Asian (SAS) AF: 0.165 AC: 14199 AN: 85878

European-Finnish (FIN) AF: 0.155 AC: 8264 AN: 53356

Middle Eastern (MID) AF: 0.239 AC: 1376 AN: 5756

European-Non Finnish (NFE) AF: 0.221 AC: 245869 AN: 1110062

Other (OTH) AF: 0.195 AC: 11731 AN: 60218

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

African (AFR) AF: 0.0401 AC: 1665 AN: 41538

American (AMR) AF: 0.315 AC: 4811 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 718 AN: 3472

East Asian (EAS) AF: 0.151 AC: 780 AN: 5168

South Asian (SAS) AF: 0.141 AC: 679 AN: 4812

European-Finnish (FIN) AF: 0.148 AC: 1562 AN: 10586

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14760 AN: 67964

Other (OTH) AF: 0.190 AC: 401 AN: 2110

Alfa AF: 0.203 Hom.: 7828

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
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
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.080	N
PhyloP100		0.13
PrimateAI	Benign	0.34	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.20
Sift	Benign	1.0	T
Sift4G	Benign	0.97	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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11611277; hg19: chr12-109826634; COSMIC: COSV60450855;