chr22-45345464-G-C
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_148674.5(SMC1B):āc.3601C>Gā(p.Pro1201Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000746 in 1,608,386 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000076 ( 0 hom. )
Consequence
SMC1B
NM_148674.5 missense
NM_148674.5 missense
Scores
2
6
7
Clinical Significance
Conservation
PhyloP100: 5.67
Genes affected
SMC1B (HGNC:11112): (structural maintenance of chromosomes 1B) SMC1L2 belongs to a family of proteins required for chromatid cohesion and DNA recombination during meiosis and mitosis (3:Revenkova et al., 2001 [PubMed 11564881]).[supplied by OMIM, Mar 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMC1B | NM_148674.5 | c.3601C>G | p.Pro1201Ala | missense_variant | 24/25 | ENST00000357450.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC1B | ENST00000357450.9 | c.3601C>G | p.Pro1201Ala | missense_variant | 24/25 | 5 | NM_148674.5 | P1 | |
SMC1B | ENST00000404354.3 | c.3379C>G | p.Pro1127Ala | missense_variant | 22/23 | 1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000803 AC: 2AN: 248976Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135120
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GnomAD4 exome AF: 0.00000755 AC: 11AN: 1456190Hom.: 0 Cov.: 28 AF XY: 0.0000110 AC XY: 8AN XY: 724756
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152196Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
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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 | Jun 11, 2021 | The c.3601C>G (p.P1201A) alteration is located in exon 24 (coding exon 24) of the SMC1B gene. This alteration results from a C to G substitution at nucleotide position 3601, causing the proline (P) at amino acid position 1201 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Benign
Sift
Uncertain
D;T
Sift4G
Benign
T;T
Vest4
MutPred
Gain of phosphorylation at Y1200 (P = 0.0772);.;
MVP
MPC
ClinPred
T
GERP RS
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