22-45389824-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_148674.5(SMC1B):c.1619G>A(p.Arg540Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000929 in 1,613,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_148674.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMC1B | NM_148674.5 | c.1619G>A | p.Arg540Gln | missense_variant | 10/25 | ENST00000357450.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC1B | ENST00000357450.9 | c.1619G>A | p.Arg540Gln | missense_variant | 10/25 | 5 | NM_148674.5 | P1 | |
SMC1B | ENST00000404354.3 | c.1619G>A | p.Arg540Gln | missense_variant | 10/23 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249444Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135336
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461752Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727176
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152082Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74274
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2024 | The c.1619G>A (p.R540Q) alteration is located in exon 10 (coding exon 10) of the SMC1B gene. This alteration results from a G to A substitution at nucleotide position 1619, causing the arginine (R) at amino acid position 540 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at