chr3-46857975-G-T

Variant names:

• chr3-46857975-G-T
• rs764865767
• NM_000258.3:c.*140C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000258.3(MYL3):​c.*140C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000489 in 408,902 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: 31)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: MYL3 NM_000258.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 0 publications found

Genes affected

MYL3 (HGNC:7584): (myosin light chain 3) MYL3 encodes myosin light chain 3, an alkali light chain also referred to in the literature as both the ventricular isoform and the slow skeletal muscle isoform. Mutations in MYL3 have been identified as a cause of mid-left ventricular chamber type hypertrophic cardiomyopathy. [provided by RefSeq, Jul 2008]

MYL3 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hypertrophic cardiomyopathy 8

  Inheritance: AD, SD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• arrhythmogenic right ventricular cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000258.3. 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
	MYL3	NM_000258.3	MANE Select	c.*140C>A		3_prime_UTR	Exon 7 of 7	NP_000249.1	P08590
	MYL3	NM_001406937.1		c.*269C>A		3_prime_UTR	Exon 6 of 6	NP_001393866.1	P08590
	MYL3	NM_001406938.1		c.*140C>A		3_prime_UTR	Exon 9 of 9	NP_001393867.1	P08590

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL3	ENST00000292327.6	TSL:1 MANE Select	c.*140C>A		3_prime_UTR	Exon 7 of 7	ENSP00000292327.4	P08590
	MYL3	ENST00000395869.5	TSL:1	c.*269C>A		3_prime_UTR	Exon 6 of 6	ENSP00000379210.1	P08590
	MYL3	ENST00000713934.1		c.*140C>A		3_prime_UTR	Exon 7 of 7	ENSP00000519231.1	A0AAQ5BH63

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000489 AC: 2 AN: 408902 Hom.: 0 Cov.: 3 AF XY: 0.00000925 AC XY: 2 AN XY: 216316

African (AFR) AF: 0.00 AC: 0 AN: 11650

American (AMR) AF: 0.00 AC: 0 AN: 18118

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12540

East Asian (EAS) AF: 0.00 AC: 0 AN: 27642

South Asian (SAS) AF: 0.00 AC: 0 AN: 45320

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1786

European-Non Finnish (NFE) AF: 0.00000822 AC: 2 AN: 243304

Other (OTH) AF: 0.00 AC: 0 AN: 23490

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.13
DANN	Benign	0.63
PhyloP100		-1.3

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: rs764865767; hg19: chr3-46899465;