22-45372213-T-A
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_148674.5(SMC1B):c.2138A>T(p.Lys713Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,612,748 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SMC1B
NM_148674.5 missense
NM_148674.5 missense
Scores
1
11
3
Clinical Significance
Conservation
PhyloP100: 1.89
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 Uncertain_significance. Variant got 4 ACMG points.
PM1
In a modified_residue N6-acetyllysine (size 0) in uniprot entity SMC1B_HUMAN
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMC1B | NM_148674.5 | c.2138A>T | p.Lys713Ile | missense_variant | 13/25 | ENST00000357450.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC1B | ENST00000357450.9 | c.2138A>T | p.Lys713Ile | missense_variant | 13/25 | 5 | NM_148674.5 | P1 | |
SMC1B | ENST00000404354.3 | c.2138A>T | p.Lys713Ile | missense_variant | 13/23 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460556Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726554
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74360
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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 | Jan 23, 2024 | The c.2138A>T (p.K713I) alteration is located in exon 13 (coding exon 13) of the SMC1B gene. This alteration results from a A to T substitution at nucleotide position 2138, causing the lysine (K) at amino acid position 713 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
T;D
Vest4
MutPred
Gain of catalytic residue at K713 (P = 0.0067);Gain of catalytic residue at K713 (P = 0.0067);
MVP
MPC
ClinPred
D
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