19-50252727-G-T

Variant names:

• chr19-50252727-G-T
• NM_001145809.2:c.1919G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001145809.2(MYH14):​c.1919G>T​(p.Arg640Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. R640Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYH14 NM_001145809.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.1919G>T	p.Arg640Leu	missense_variant	Exon 16 of 43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.1919G>T	p.Arg640Leu	missense_variant	Exon 16 of 42		NP_001070654.1
MYH14	NM_024729.4	c.1895G>T	p.Arg632Leu	missense_variant	Exon 15 of 41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.1919G>T	p.Arg640Leu	missense_variant	Exon 16 of 43		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1443324 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 716224

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.057	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.60	.;.;D;.;D;.;D
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.072
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.91	.;D;D;.;D;D;.
M_CAP	Uncertain	0.16	D
MetaRNN	Uncertain	0.44	T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	0.88	.;.;L;.;.;.;L
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.0	.;D;D;.;.;.;.
REVEL	Uncertain	0.41
Sift	Uncertain	0.019	.;D;T;.;.;.;.
Sift4G	Benign	0.10	T;T;T;.;T;T;T
Polyphen		0.31	B;B;B;B;.;B;B
Vest4		0.59
MutPred		0.51		.;.;Loss of phosphorylation at T630 (P = 0.0738);.;.;.;Loss of phosphorylation at T630 (P = 0.0738);
MVP		0.82
MPC		0.58
ClinPred		0.54	D
GERP RS		2.2
Varity_R		0.21
gMVP		0.59

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-50755984;