chr12-109386921-G-A

Variant names:

• chr12-109386921-G-A
• rs10850110
• NM_001101421.4:c.13-1762G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001101421.4(MYO1H):​c.13-1762G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 151,250 control chromosomes in the GnomAD database, including 2,867 homozygotes. In-silico tool predicts 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 (2867 hom., cov: 32)
• Consequence: MYO1H NM_001101421.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 19 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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1H	NM_001101421.4	c.13-1762G>A		intron_variant	Intron 1 of 31	ENST00000310903.10	NP_001094891.4
MYO1H	XM_011538223.3	c.-36-1762G>A		intron_variant	Intron 2 of 33		XP_011536525.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1H	ENST00000310903.10	c.13-1762G>A		intron_variant	Intron 1 of 31	5	NM_001101421.4	ENSP00000439182.2

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25682 AN: 151132 Hom.: 2869 Cov.: 32

Gnomad AFR AF: 0.0404

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.193

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.170 AC: 25672 AN: 151250 Hom.: 2867 Cov.: 32 AF XY: 0.169 AC XY: 12443 AN XY: 73826

African (AFR) AF: 0.0403 AC: 1660 AN: 41210

American (AMR) AF: 0.317 AC: 4822 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3468

East Asian (EAS) AF: 0.147 AC: 755 AN: 5140

South Asian (SAS) AF: 0.142 AC: 680 AN: 4788

European-Finnish (FIN) AF: 0.152 AC: 1561 AN: 10280

Middle Eastern (MID) AF: 0.210 AC: 61 AN: 290

European-Non Finnish (NFE) AF: 0.218 AC: 14782 AN: 67864

Other (OTH) AF: 0.192 AC: 403 AN: 2100

Alfa AF: 0.212 Hom.: 3072

Bravo AF: 0.179

Asia WGS AF: 0.142 AC: 496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.77
DANN	Benign	0.34
PhyloP100		0.040
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10850110; hg19: chr12-109824726;