rs3825393

Variant names:

• chr12-109445569-T-C
• rs3825393
• NM_001101421.4:c.3050T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-109445569-T-C
• chr12-109445569-T-A
• chr12-109445569-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001101421.4(MYO1H):​c.3050T>C​(p.Leu1017Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 1,610,944 control chromosomes in the GnomAD database, including 347,915 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.71 (40130 hom., cov: 32)
  • Exomes 𝑓: 0.65 (307785 hom.)
• Consequence: MYO1H NM_001101421.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0330
• Publications: 45 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)

ENSG00000255655 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.0434917E-7).
• BP6: Variant 12-109445569-T-C is Benign according to our data. Variant chr12-109445569-T-C is described in ClinVar as Benign. ClinVar VariationId is 1267555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 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.3050T>C	p.Leu1017Pro	missense	Exon 31 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.3050T>C	p.Leu1017Pro	missense	Exon 31 of 32	ENSP00000439182.2	A0A140TA25
	ENSG00000255655	ENST00000539987.1	TSL:3	n.444A>G		non_coding_transcript_exon	Exon 2 of 2
	MYO1H	ENST00000542268.5	TSL:2	n.850T>C		non_coding_transcript_exon	Exon 8 of 9

Frequencies

GnomAD3 genomes AF: 0.712 AC: 108166 AN: 151982 Hom.: 40072 Cov.: 32

Gnomad AFR AF: 0.931

Gnomad AMI AF: 0.718

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.700

GnomAD2 exomes AF: 0.644 AC: 159137 AN: 247116 AF XY: 0.649

Gnomad AFR exome AF: 0.938

Gnomad AMR exome AF: 0.528

Gnomad ASJ exome AF: 0.681

Gnomad EAS exome AF: 0.505

Gnomad FIN exome AF: 0.553

Gnomad NFE exome AF: 0.657

Gnomad OTH exome AF: 0.639

GnomAD4 exome AF: 0.645 AC: 941597 AN: 1458844 Hom.: 307785 Cov.: 43 AF XY: 0.648 AC XY: 470419 AN XY: 725596

African (AFR) AF: 0.943 AC: 31496 AN: 33396

American (AMR) AF: 0.542 AC: 24048 AN: 44378

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 17595 AN: 26086

East Asian (EAS) AF: 0.473 AC: 18760 AN: 39620

South Asian (SAS) AF: 0.711 AC: 60854 AN: 85618

European-Finnish (FIN) AF: 0.558 AC: 29680 AN: 53212

Middle Eastern (MID) AF: 0.750 AC: 4323 AN: 5762

European-Non Finnish (NFE) AF: 0.644 AC: 715478 AN: 1110518

Other (OTH) AF: 0.653 AC: 39363 AN: 60254

GnomAD4 genome AF: 0.712 AC: 108281 AN: 152100 Hom.: 40130 Cov.: 32 AF XY: 0.702 AC XY: 52156 AN XY: 74326

African (AFR) AF: 0.931 AC: 38660 AN: 41536

American (AMR) AF: 0.591 AC: 9031 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2338 AN: 3470

East Asian (EAS) AF: 0.502 AC: 2600 AN: 5184

South Asian (SAS) AF: 0.692 AC: 3325 AN: 4808

European-Finnish (FIN) AF: 0.550 AC: 5796 AN: 10538

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44188 AN: 67974

Other (OTH) AF: 0.700 AC: 1476 AN: 2110

Alfa AF: 0.666 Hom.: 146398

Bravo AF: 0.724

TwinsUK AF: 0.646 AC: 2395

ALSPAC AF: 0.633 AC: 2441

ESP6500AA AF: 0.920 AC: 3399

ESP6500EA AF: 0.644 AC: 5268

ExAC AF: 0.658 AC: 79488

Asia WGS AF: 0.606 AC: 2107 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	13
DANN	Benign	0.62
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.0071	T
MetaRNN	Benign	6.0e-7	T
MetaSVM	Benign	-0.99	T
PhyloP100		0.033
PrimateAI	Benign	0.28	T
REVEL	Benign	0.030
Sift4G	Benign	0.43	T
Vest4		0.028
MPC		0.13
ClinPred		0.00085	T
GERP RS		2.8
gMVP		0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3825393; hg19: chr12-109883374; COSMIC: COSV57326253; COSMIC: COSV57326253;