rs201986144

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_001145809.2(MYH14):​c.5990C>A​(p.Thr1997Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,458,962 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: 29)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

MYH14
NM_001145809.2 missense

Scores

1
4
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.35
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.14999995).
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00000754 (11/1458962) while in subpopulation MID AF= 0.00139 (8/5764). AF 95% confidence interval is 0.00069. There are 0 homozygotes in gnomad4_exome. There are 7 alleles in male gnomad4_exome subpopulation. Median coverage is 35. This position pass quality control queck.
BS2
High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MYH14NM_001145809.2 linkuse as main transcriptc.5990C>A p.Thr1997Lys missense_variant 43/43 ENST00000642316.2 NP_001139281.1
MYH14NM_001077186.2 linkuse as main transcriptc.5891C>A p.Thr1964Lys missense_variant 42/42 NP_001070654.1
MYH14NM_024729.4 linkuse as main transcriptc.5867C>A p.Thr1956Lys missense_variant 41/41 NP_079005.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MYH14ENST00000642316.2 linkuse as main transcriptc.5990C>A p.Thr1997Lys missense_variant 43/43 NM_001145809.2 ENSP00000493594 Q7Z406-2

Frequencies

GnomAD3 genomes
Cov.:
29
GnomAD3 exomes
AF:
0.00000826
AC:
2
AN:
242058
Hom.:
0
AF XY:
0.00000760
AC XY:
1
AN XY:
131516
show subpopulations
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:
0.00
Gnomad OTH exome
AF:
0.000339
GnomAD4 exome
AF:
0.00000754
AC:
11
AN:
1458962
Hom.:
0
Cov.:
35
AF XY:
0.00000965
AC XY:
7
AN XY:
725482
show subpopulations
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:
0.0000351
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
29
Alfa
AF:
0.0000106
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.40
BayesDel_addAF
Uncertain
0.043
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
20
DANN
Benign
0.97
DEOGEN2
Benign
0.13
.;.;.;T;.;.;T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.40
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.67
.;T;T;T;.;T;.
M_CAP
Uncertain
0.13
D
MetaRNN
Benign
0.15
T;T;T;T;T;T;T
MetaSVM
Benign
-0.63
T
MutationAssessor
Benign
1.4
.;.;.;L;.;.;L
MutationTaster
Benign
1.0
N;N;N;N
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-1.1
.;.;N;.;.;.;.
REVEL
Uncertain
0.31
Sift
Benign
0.67
.;.;T;.;.;.;.
Sift4G
Benign
0.78
T;T;T;T;.;T;T
Polyphen
0.59
P;.;P;B;P;P;B
Vest4
0.29
MutPred
0.21
.;.;.;Gain of methylation at T1956 (P = 0.0196);.;.;Gain of methylation at T1956 (P = 0.0196);
MVP
0.87
MPC
0.19
ClinPred
0.11
T
GERP RS
3.8
Varity_R
0.18
gMVP
0.51

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201986144; hg19: chr19-50812926; API