chr12-57028736-T-C

Variant names:

• chr12-57028736-T-C
• rs201677711
• ENST00000300119:c.*19A>G

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.*19A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000762 in 1,613,684 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00060 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00078 (6 hom.)
• Consequence: MYO1A NM_005379.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.243

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]

TAC3 (HGNC:11521): (tachykinin precursor 3) This gene encodes a member of the tachykinin family of secreted neuropeptides. The encoded preproprotein is proteolytically processed to generate the mature peptide, which is primarily expressed in the central and peripheral nervous systems and functions as a neurotransmitter. This peptide is the ligand for the neurokinin-3 receptor. This protein is also expressed in the outer syncytiotrophoblast of the placenta and may be associated with pregnancy-induced hypertension and pre-eclampsia. Mutations in this gene are associated with normosmic hypogonadotropic hypogonadism. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-57028736-T-C is Benign according to our data. Variant chr12-57028736-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1318916.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 92 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYO1A	NM_005379.4	c.*19A>G		3_prime_UTR_variant	Exon 28 of 28	ENST00000300119.8	NP_005370.1
MYO1A	NM_001256041.2	c.*19A>G		3_prime_UTR_variant	Exon 29 of 29		NP_001242970.1
MYO1A	XM_047428876.1	c.*19A>G		3_prime_UTR_variant	Exon 29 of 29		XP_047284832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYO1A	ENST00000300119	c.*19A>G		3_prime_UTR_variant	Exon 28 of 28	1	NM_005379.4	ENSP00000300119.3

Frequencies

GnomAD3 genomes AF: 0.000605 AC: 92 AN: 152098 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00312

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000941

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000686 AC: 172 AN: 250636 AF XY: 0.000864

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000857

Gnomad OTH exome AF: 0.000819

GnomAD4 exome AF: 0.000778 AC: 1137 AN: 1461468 Hom.: 6 Cov.: 31 AF XY: 0.000865 AC XY: 629 AN XY: 727024

Gnomad4 AFR exome AF: 0.0000896 AC: 3 AN: 33480

Gnomad4 AMR exome AF: 0.000313 AC: 14 AN: 44716

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26058

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.00211 AC: 182 AN: 86196

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 53394

Gnomad4 NFE exome AF: 0.000766 AC: 852 AN: 1111770

Gnomad4 Remaining exome AF: 0.000927 AC: 56 AN: 60386

GnomAD4 genome AF: 0.000604 AC: 92 AN: 152216 Hom.: 0 Cov.: 31 AF XY: 0.000645 AC XY: 48 AN XY: 74408

Gnomad4 AFR AF: 0.0000722 AC: 0.0000722369 AN: 0.0000722369

Gnomad4 AMR AF: 0.000458 AC: 0.000457756 AN: 0.000457756

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00312 AC: 0.0031198 AN: 0.0031198

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000941 AC: 0.00094101 AN: 0.00094101

Gnomad4 OTH AF: 0.000946 AC: 0.000946074 AN: 0.000946074

Alfa AF: 0.000598 Hom.: 0

Bravo AF: 0.000499

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 20, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.55
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

Publications

LitVar

Other links and lift over

dbSNP: rs201677711; hg19: chr12-57422520;