rs3825393

chr12-109445569-T-Cchr12-109445569-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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. 11/15 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, single submitter B:1
• Conservation: PhyloP100: 0.0330

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1267555.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.923 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYO1H	NM_001101421.4	c.3050T>C	p.Leu1017Pro	missense_variant	31/32	ENST00000310903.10
MYO1H	XM_011538223.3	c.3068T>C	p.Leu1023Pro	missense_variant	33/34
MYO1H	XM_047428738.1	c.3002T>C	p.Leu1001Pro	missense_variant	30/31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYO1H	ENST00000310903.10	c.3050T>C	p.Leu1017Pro	missense_variant	31/32	5	NM_001101421.4	P1
	ENST00000539987.1	n.444A>G		non_coding_transcript_exon_variant	2/2	3
MYO1H	ENST00000542268.5	n.850T>C		non_coding_transcript_exon_variant	8/9	2
MYO1H	ENST00000543960.1	c.314T>C	p.Leu105Pro	missense_variant, NMD_transcript_variant	4/6	4

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

GnomAD3 exomes AF: 0.644 AC: 159137 AN: 247116 Hom.: 52658 AF XY: 0.649 AC XY: 86954 AN XY: 134028

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 SAS exome AF: 0.712

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

Gnomad4 AFR exome AF: 0.943

Gnomad4 AMR exome AF: 0.542

Gnomad4 ASJ exome AF: 0.674

Gnomad4 EAS exome AF: 0.473

Gnomad4 SAS exome AF: 0.711

Gnomad4 FIN exome AF: 0.558

Gnomad4 NFE exome AF: 0.644

Gnomad4 OTH exome AF: 0.653

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

Gnomad4 AFR AF: 0.931

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.502

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.700

Alfa AF: 0.656 Hom.: 71855

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

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 18, 2020

This variant is associated with the following publications: (PMID: 29986156) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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;T
MetaRNN	Benign	6.0e-7	T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.28	T
REVEL	Benign	0.030
Sift4G	Benign	0.43	T;T
Vest4		0.028
MPC		0.13
ClinPred		0.00085	T
GERP RS		2.8
gMVP		0.15

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

Publications

LitVar

Other links and lift over

dbSNP: rs3825393; hg19: chr12-109883374; COSMIC: COSV57326253; COSMIC: COSV57326253;