12-109421295-A-G

Position:

• chr12-109421295-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001101421.4(MYO1H):​c.1644+268A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,874 control chromosomes in the GnomAD database, including 20,456 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 0.51 (20456 hom., cov: 31)
• Consequence: MYO1H NM_001101421.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYO1H	NM_001101421.4	c.1644+268A>G		intron_variant		ENST00000310903.10	NP_001094891.4
MYO1H	XM_011538223.3	c.1596+268A>G		intron_variant			XP_011536525.1
MYO1H	XM_047428738.1	c.1596+268A>G		intron_variant			XP_047284694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYO1H	ENST00000310903.10	c.1644+268A>G		intron_variant		5	NM_001101421.4	ENSP00000439182.2

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77095 AN: 151756 Hom.: 20422 Cov.: 31

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.530

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

GnomAD4 genome AF: 0.508 AC: 77185 AN: 151874 Hom.: 20456 Cov.: 31 AF XY: 0.503 AC XY: 37292 AN XY: 74212

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.528

Alfa AF: 0.502 Hom.: 3181

Bravo AF: 0.536

Asia WGS AF: 0.380 AC: 1323 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs2075440; hg19: chr12-109859100; COSMIC: COSV60451216;