rs137975387

Variant names:

• chr12-57044168-G-A
• rs137975387
• NM_005379.4:c.682C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-57044168-G-A
• chr12-57044168-G-C
• chr12-57044168-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_005379.4(MYO1A):​c.682C>T​(p.Leu228Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000684 in 1,461,838 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: MYO1A NM_005379.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.39
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1A	NM_005379.4	c.682C>T	p.Leu228Leu	synonymous_variant	Exon 9 of 28	ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2	c.682C>T	p.Leu228Leu	synonymous_variant	Exon 10 of 29		NP_001242970.1
MYO1A	XM_047428876.1	c.682C>T	p.Leu228Leu	synonymous_variant	Exon 10 of 29		XP_047284832.1
MYO1A	XM_011538373.3	c.682C>T	p.Leu228Leu	synonymous_variant	Exon 9 of 25		XP_011536675.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1A	ENST00000300119.8	c.682C>T	p.Leu228Leu	synonymous_variant	Exon 9 of 28	1	NM_005379.4	ENSP00000300119.3
MYO1A	ENST00000442789.6	c.682C>T	p.Leu228Leu	synonymous_variant	Exon 10 of 29	1		ENSP00000393392.2
MYO1A	ENST00000554234.5	n.196C>T		non_coding_transcript_exon_variant	Exon 5 of 24	5		ENSP00000451033.1
MYO1A	ENST00000492945.5	c.-20-810C>T		intron_variant	Intron 2 of 4	4		ENSP00000452229.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461838 Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.6
DANN	Benign	0.38
PhyloP100		6.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs137975387; hg19: chr12-57437952;