19-50231990-C-T

Variant names:

• chr19-50231990-C-T
• rs35315400
• NM_001145809.2:c.1034C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_001145809.2(MYH14):​c.1034C>T​(p.Ser345Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 0.0000075 (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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21161985).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.1034C>T	p.Ser345Phe	missense_variant	Exon 10 of 43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.1034C>T	p.Ser345Phe	missense_variant	Exon 10 of 42		NP_001070654.1
MYH14	NM_024729.4	c.1010C>T	p.Ser337Phe	missense_variant	Exon 9 of 41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.1034C>T	p.Ser345Phe	missense_variant	Exon 10 of 43		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248998 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135128

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461560 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727058

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: 0.00000989

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	.;.;T;.;T;.;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.58	.;T;T;.;T;T;.
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.21	T;T;T;T;T;T;T
MetaSVM	Benign	-0.46	T
MutationAssessor	Benign	0.81	.;.;L;.;.;.;L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.68	.;N;N;.;.;.;.
REVEL	Benign	0.23
Sift	Uncertain	0.0040	.;D;D;.;.;.;.
Sift4G	Uncertain	0.023	D;D;D;.;D;D;D
Polyphen		0.79	P;P;P;P;.;P;P
Vest4		0.27
MutPred		0.44		.;.;Loss of phosphorylation at S337 (P = 0.0274);.;.;.;Loss of phosphorylation at S337 (P = 0.0274);
MVP		0.47
MPC		0.53
ClinPred		0.58	D
GERP RS		3.0
Varity_R		0.14
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs35315400; hg19: chr19-50735247;