rs375866139

Variant names:

• chr19-50286559-T-C
• rs375866139
• NM_001145809.2:c.4617T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-50286559-T-C
• chr19-50286559-T-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001145809.2(MYH14):​c.4617T>C​(p.Arg1539Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,674 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: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MYH14 NM_001145809.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357

Genes affected

MYH14 (HGNC:23212): (myosin heavy chain 14) This gene encodes a member of the myosin superfamily. The protein represents a conventional non-muscle myosin; it should not be confused with the unconventional myosin-14 (MYO14). Myosins are actin-dependent motor proteins with diverse functions including regulation of cytokinesis, cell motility, and cell polarity. Mutations in this gene result in one form of autosomal dominant hearing impairment. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05400151).
• BP7: Synonymous conserved (PhyloP=-0.357 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.4617T>C	p.Arg1539Arg	synonymous_variant	Exon 34 of 43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.4518T>C	p.Arg1506Arg	synonymous_variant	Exon 33 of 42		NP_001070654.1
MYH14	NM_024729.4	c.4494T>C	p.Arg1498Arg	synonymous_variant	Exon 32 of 41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.4617T>C	p.Arg1539Arg	synonymous_variant	Exon 34 of 43		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459674 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725858

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.42
DANN	Benign	0.70
DEOGEN2	Benign	0.018	T
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.054	T
Sift4G	Benign	0.75	T
Vest4		0.054
MVP		0.52
GERP RS		-9.1

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: rs375866139; hg19: chr19-50789816;