rs202207957

Variant names:

• chr12-57029304-C-T
• rs202207957
• NM_005379.4:c.2878-45G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_005379.4(MYO1A):​c.2878-45G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00279 in 1,613,508 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (16 hom.)
• Consequence: MYO1A NM_005379.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.457
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 12-57029304-C-T is Benign according to our data. Variant chr12-57029304-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1326653.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 352 AD gene.

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.2878-45G>A		intron	N/A	NP_005370.1	Q9UBC5
	MYO1A	NM_001256041.2		c.2878-45G>A		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.2878-45G>A		intron	N/A	ENSP00000300119.3	Q9UBC5
	MYO1A	ENST00000442789.6	TSL:1	c.2878-45G>A		intron	N/A	ENSP00000393392.2	Q9UBC5
	MYO1A	ENST00000907120.1		c.3010-45G>A		intron	N/A	ENSP00000577179.1

Frequencies

GnomAD3 genomes AF: 0.00231 AC: 352 AN: 152082 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.00426

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00343

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00215 AC: 537 AN: 249508 AF XY: 0.00218

Gnomad AFR exome AF: 0.000255

Gnomad AMR exome AF: 0.00443

Gnomad ASJ exome AF: 0.000796

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000473

Gnomad NFE exome AF: 0.00303

Gnomad OTH exome AF: 0.00379

GnomAD4 exome AF: 0.00284 AC: 4152 AN: 1461308 Hom.: 16 Cov.: 33 AF XY: 0.00273 AC XY: 1984 AN XY: 726972

African (AFR) AF: 0.000418 AC: 14 AN: 33478

American (AMR) AF: 0.00463 AC: 207 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000995 AC: 26 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86246

European-Finnish (FIN) AF: 0.0000378 AC: 2 AN: 52872

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5766

European-Non Finnish (NFE) AF: 0.00330 AC: 3672 AN: 1112000

Other (OTH) AF: 0.00316 AC: 191 AN: 60386

GnomAD4 genome AF: 0.00231 AC: 352 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.00219 AC XY: 163 AN XY: 74394

African (AFR) AF: 0.000530 AC: 22 AN: 41540

American (AMR) AF: 0.00425 AC: 65 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00343 AC: 233 AN: 67978

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00325 Hom.: 0

Bravo AF: 0.00271

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.5
DANN	Benign	0.49
PhyloP100		0.46
PromoterAI		0.00090	Neutral
Mutation Taster		=100/0	polymorphism

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: rs202207957; hg19: chr12-57423088;