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GeneBe

2-127048530-G-A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PM2_SupportingBP4_Moderate

The NM_139343.3(BIN1):c.1778C>T(p.Pro593Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

BIN1
NM_139343.3 missense

Scores

2
3
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.23

Links

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM2
?
Very rare variant; Number of alleles below threshold, Median coverage is 33.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.18247545).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BIN1NM_139343.3 linkuse as main transcriptc.1778C>T p.Pro593Leu missense_variant 19/19 ENST00000316724.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BIN1ENST00000316724.10 linkuse as main transcriptc.1778C>T p.Pro593Leu missense_variant 19/191 NM_139343.3 O00499-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250228
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135362
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:
0.0000267
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461602
Hom.:
0
AF XY:
0.00000688
AC XY:
5
AN XY:
727098
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.0000166
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000247
AC:
3

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Myopathy, centronuclear, 2 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingRevvity Omics, Revvity OmicsDec 16, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.33
Cadd
Benign
23
Dann
Uncertain
0.99
Eigen
Benign
-0.27
Eigen_PC
Benign
-0.26
FATHMM_MKL
Benign
0.37
N
LIST_S2
Uncertain
0.95
D;D;D;D;D;D;D;D;D;D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.18
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.95
T
MutationTaster
Benign
0.98
N;N;N;N;N;N;N;N;N;N;N
PrimateAI
Benign
0.41
T
PROVEAN
Benign
-2.1
N;N;N;N;N;N;N;N;N;N;N
REVEL
Benign
0.17
Sift
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
D;D;D;D;D;D;D;D;B;D;D
Vest4
0.30
MVP
0.63
MPC
0.93
ClinPred
0.62
D
GERP RS
2.5
Varity_R
0.11
gMVP
0.23

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

LitVar

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

Other links and lift over

dbSNP: rs375004668; hg19: chr2-127806106; API