1-109295188-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001010985.3(MYBPHL):āc.977T>Cā(p.Phe326Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000263 in 1,614,024 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000085 ( 0 hom., cov: 32)
Exomes š: 0.00028 ( 0 hom. )
Consequence
MYBPHL
NM_001010985.3 missense
NM_001010985.3 missense
Scores
3
9
7
Clinical Significance
Conservation
PhyloP100: 4.83
Genes affected
MYBPHL (HGNC:30434): (myosin binding protein H like) This gene encodes a protein with two immunoglobulin superfamily domains and a fibronectin 3 domain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2012]
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ACMG classification
Classification made for transcript
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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYBPHL | NM_001010985.3 | c.977T>C | p.Phe326Ser | missense_variant | 7/9 | ENST00000357155.2 | NP_001010985.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYBPHL | ENST00000357155.2 | c.977T>C | p.Phe326Ser | missense_variant | 7/9 | 1 | NM_001010985.3 | ENSP00000349678 | P1 | |
MYBPHL | ENST00000477962.1 | n.259T>C | non_coding_transcript_exon_variant | 2/4 | 1 | |||||
MYBPHL | ENST00000489706.5 | n.230T>C | non_coding_transcript_exon_variant | 2/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000854 AC: 13AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000187 AC: 47AN: 251358Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135848
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GnomAD4 exome AF: 0.000281 AC: 411AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.000293 AC XY: 213AN XY: 727232
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GnomAD4 genome AF: 0.0000854 AC: 13AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74352
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 02, 2021 | The c.977T>C (p.F326S) alteration is located in exon 7 (coding exon 7) of the MYBPHL gene. This alteration results from a T to C substitution at nucleotide position 977, causing the phenylalanine (F) at amino acid position 326 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Pathogenic
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at