chr22-45352546-G-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_148674.5(SMC1B):c.3330C>A(p.Asn1110Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,732 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SMC1B
NM_148674.5 missense
NM_148674.5 missense
Scores
2
7
6
Clinical Significance
Conservation
PhyloP100: 3.46
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 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 |
---|---|---|---|---|---|---|---|---|
SMC1B | NM_148674.5 | c.3330C>A | p.Asn1110Lys | missense_variant | 22/25 | ENST00000357450.9 | NP_683515.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMC1B | ENST00000357450.9 | c.3330C>A | p.Asn1110Lys | missense_variant | 22/25 | 5 | NM_148674.5 | ENSP00000350036.4 | ||
SMC1B | ENST00000404354.3 | c.3273+1432C>A | intron_variant | 1 | ENSP00000385902.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461732Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727172
GnomAD4 exome
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2
AN:
1461732
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32
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2
AN XY:
727172
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 | Mar 30, 2022 | The c.3330C>A (p.N1110K) alteration is located in exon 22 (coding exon 22) of the SMC1B gene. This alteration results from a C to A substitution at nucleotide position 3330, causing the asparagine (N) at amino acid position 1110 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Vest4
MutPred
Gain of methylation at N1110 (P = 0.0162);
MVP
MPC
ClinPred
D
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.