chr6-41931475-G-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_004053.4(BYSL):c.784G>A(p.Val262Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,613,888 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000023 ( 1 hom. )
Consequence
BYSL
NM_004053.4 missense
NM_004053.4 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 7.19
Genes affected
BYSL (HGNC:1157): (bystin like) Bystin is expressed as a 2-kb major transcript and a 3.6-kb minor transcript in SNG-M cells and in human trophoblastic teratocarcinoma HT-H cells. Protein binding assays determined that bystin binds directly to trophinin and tastin, and that binding is enhanced when cytokeratins 8 and 18 are present. Immunocytochemistry of HT-H cells showed that bystin colocalizes with trophinin, tastin, and the cytokeratins, suggesting that these molecules form a complex in trophectoderm cells at the time of implantation. Using immunohistochemistry it was determined that trophinin and bystin are found in the placenta from the sixth week of pregnancy. Both proteins were localized in the cytoplasm of the syncytiotrophoblast in the chorionic villi and in endometrial decidual cells at the uteroplacental interface. After week 10, the levels of trophinin, tastin, and bystin decreased and then disappeared from placental villi. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.021629691).
BP6
Variant 6-41931475-G-A is Benign according to our data. Variant chr6-41931475-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2387907.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BYSL | NM_004053.4 | c.784G>A | p.Val262Ile | missense_variant | 5/7 | ENST00000230340.9 | NP_004044.3 | |
BYSL | XM_047419281.1 | c.538G>A | p.Val180Ile | missense_variant | 5/7 | XP_047275237.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BYSL | ENST00000230340.9 | c.784G>A | p.Val262Ile | missense_variant | 5/7 | 1 | NM_004053.4 | ENSP00000230340 | P1 | |
BYSL | ENST00000372996.2 | c.457G>A | p.Val153Ile | missense_variant, NMD_transcript_variant | 4/6 | 5 | ENSP00000362087 | |||
BYSL | ENST00000489290.1 | c.*60G>A | 3_prime_UTR_variant, NMD_transcript_variant | 4/6 | 3 | ENSP00000417813 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152120Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251484Hom.: 1 AF XY: 0.0000736 AC XY: 10AN XY: 135918
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GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461768Hom.: 1 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 727204
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74316
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 10, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
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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