rs28940306

Variant names:

• chr19-50271424-C-G
• NM_001145809.2:c.3049C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-50271424-C-G
• chr19-50271424-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM5

The NM_001145809.2(MYH14):​c.3049C>G​(p.Leu1017Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,368 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1017F) has been classified as Pathogenic.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MYH14 NM_001145809.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.18

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr19-50271424-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.3049C>G	p.Leu1017Val	missense_variant	Exon 25 of 43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.2950C>G	p.Leu984Val	missense_variant	Exon 24 of 42		NP_001070654.1
MYH14	NM_024729.4	c.2926C>G	p.Leu976Val	missense_variant	Exon 23 of 41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.3049C>G	p.Leu1017Val	missense_variant	Exon 25 of 43		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452368 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 721498

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.03e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.55	.;.;D;.;T;.;D
Eigen	Benign	0.014
Eigen_PC	Benign	-0.055
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.79	.;T;T;.;D;T;.
M_CAP	Benign	0.066	D
MetaRNN	Uncertain	0.56	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Benign	1.5	.;.;L;.;.;.;L
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-2.6	.;D;.;.;.;.;.
REVEL	Uncertain	0.43
Sift	Uncertain	0.020	.;D;.;.;.;.;.
Sift4G	Benign	0.11	T;T;T;.;T;T;T
Polyphen		0.77	P;P;P;P;.;P;P
Vest4		0.61
MutPred		0.59		.;.;Gain of helix (P = 0.0861);.;.;.;Gain of helix (P = 0.0861);
MVP		0.66
MPC		0.36
ClinPred		0.86	D
GERP RS		2.5
Varity_R		0.065
gMVP		0.20

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-50774681;