rs9943753

Variant names:

• chr12-109403135-A-G
• rs9943753
• NM_001101421.4:c.751-847A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-109403135-A-G
• chr12-109403135-A-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.751-847A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.711 in 152,194 control chromosomes in the GnomAD database, including 39,996 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 0.71 (39996 hom., cov: 33)
• Consequence: MYO1H NM_001101421.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 27 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.919 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1H	NM_001101421.4	c.751-847A>G		intron_variant	Intron 6 of 31	ENST00000310903.10	NP_001094891.4
MYO1H	XM_011538223.3	c.703-847A>G		intron_variant	Intron 7 of 33		XP_011536525.1
MYO1H	XM_047428738.1	c.703-847A>G		intron_variant	Intron 5 of 30		XP_047284694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1H	ENST00000310903.10	c.751-847A>G		intron_variant	Intron 6 of 31	5	NM_001101421.4	ENSP00000439182.2
MYO1H	ENST00000542883.1	n.81-847A>G		intron_variant	Intron 1 of 4	4

Frequencies

GnomAD3 genomes AF: 0.711 AC: 108159 AN: 152076 Hom.: 39930 Cov.: 33

Gnomad AFR AF: 0.926

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.711 AC: 108283 AN: 152194 Hom.: 39996 Cov.: 33 AF XY: 0.704 AC XY: 52354 AN XY: 74396

African (AFR) AF: 0.926 AC: 38493 AN: 41552

American (AMR) AF: 0.684 AC: 10440 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2414 AN: 3472

East Asian (EAS) AF: 0.519 AC: 2686 AN: 5178

South Asian (SAS) AF: 0.645 AC: 3108 AN: 4822

European-Finnish (FIN) AF: 0.559 AC: 5912 AN: 10582

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42929 AN: 68004

Other (OTH) AF: 0.704 AC: 1488 AN: 2114

Alfa AF: 0.681 Hom.: 68256

Bravo AF: 0.732

Asia WGS AF: 0.612 AC: 2127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.0
DANN	Benign	0.27
PhyloP100		0.040
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: rs9943753; hg19: chr12-109840940;