NM_005379.4:c.2877+22A>G

Variant names:

• chr12-57029413-T-C
• rs56128678
• NM_005379.4:c.2877+22A>G

Variant summary

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

The NM_005379.4(MYO1A):​c.2877+22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0872 in 1,613,792 control chromosomes in the GnomAD database, including 6,481 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (787 hom., cov: 32)
  • Exomes 𝑓: 0.086 (5694 hom.)
• Consequence: MYO1A NM_005379.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.290
• Publications: 5 publications found

Genes affected

MYO1A (HGNC:7595): (myosin IA) This gene encodes a member of the myosin superfamily. The protein represents an unconventional myosin; it should not be confused with the conventional skeletal muscle myosin-1 (MYH1). Unconventional myosins contain the basic domains characteristic of conventional myosins and are further distinguished from class members by their tail domains. They function as actin-based molecular motors. Mutations in this gene have been associated with autosomal dominant deafness. Alternatively spliced variants have been found for this gene. [provided by RefSeq, Dec 2011]

MYO1A Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 12-57029413-T-C is Benign according to our data. Variant chr12-57029413-T-C is described in ClinVar as Benign. ClinVar VariationId is 1289007.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005379.4. 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
	MYO1A	NM_005379.4	MANE Select	c.2877+22A>G		intron	N/A	NP_005370.1	Q9UBC5
	MYO1A	NM_001256041.2		c.2877+22A>G		intron	N/A	NP_001242970.1	Q9UBC5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYO1A	ENST00000300119.8	TSL:1 MANE Select	c.2877+22A>G		intron	N/A	ENSP00000300119.3	Q9UBC5
	MYO1A	ENST00000442789.6	TSL:1	c.2877+22A>G		intron	N/A	ENSP00000393392.2	Q9UBC5
	MYO1A	ENST00000907120.1		c.3009+22A>G		intron	N/A	ENSP00000577179.1

Frequencies

GnomAD3 genomes AF: 0.0986 AC: 14977 AN: 151930 Hom.: 786 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.0747

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0812

Gnomad OTH AF: 0.0852

GnomAD2 exomes AF: 0.0974 AC: 24464 AN: 251208 AF XY: 0.0967

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.0899

Gnomad ASJ exome AF: 0.0763

Gnomad EAS exome AF: 0.186

Gnomad FIN exome AF: 0.103

Gnomad NFE exome AF: 0.0842

Gnomad OTH exome AF: 0.0897

GnomAD4 exome AF: 0.0860 AC: 125770 AN: 1461744 Hom.: 5694 Cov.: 33 AF XY: 0.0858 AC XY: 62412 AN XY: 727178

African (AFR) AF: 0.111 AC: 3731 AN: 33478

American (AMR) AF: 0.0921 AC: 4120 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0742 AC: 1940 AN: 26136

East Asian (EAS) AF: 0.139 AC: 5528 AN: 39698

South Asian (SAS) AF: 0.100 AC: 8660 AN: 86254

European-Finnish (FIN) AF: 0.102 AC: 5449 AN: 53384

Middle Eastern (MID) AF: 0.0907 AC: 520 AN: 5736

European-Non Finnish (NFE) AF: 0.0814 AC: 90520 AN: 1111946

Other (OTH) AF: 0.0878 AC: 5302 AN: 60388

GnomAD4 genome AF: 0.0986 AC: 14999 AN: 152048 Hom.: 787 Cov.: 32 AF XY: 0.101 AC XY: 7530 AN XY: 74330

African (AFR) AF: 0.110 AC: 4567 AN: 41488

American (AMR) AF: 0.122 AC: 1866 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0747 AC: 259 AN: 3466

East Asian (EAS) AF: 0.181 AC: 932 AN: 5150

South Asian (SAS) AF: 0.106 AC: 509 AN: 4818

European-Finnish (FIN) AF: 0.104 AC: 1098 AN: 10572

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0812 AC: 5518 AN: 67970

Other (OTH) AF: 0.0866 AC: 183 AN: 2112

Alfa AF: 0.0836 Hom.: 95

Bravo AF: 0.0989

Asia WGS AF: 0.139 AC: 480 AN: 3478

ClinVar

ClinVar submissions as Germline

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
BayesDel_noAF	Benign	-0.91
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		-0.29
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: rs56128678; hg19: chr12-57423197;