chr22-45345485-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_148674.5(SMC1B):c.3580G>A(p.Asp1194Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D1194D) has been classified as Benign.
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.3580G>A | p.Asp1194Asn | missense_variant | 24/25 | ENST00000357450.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC1B | ENST00000357450.9 | c.3580G>A | p.Asp1194Asn | missense_variant | 24/25 | 5 | NM_148674.5 | P1 | |
SMC1B | ENST00000404354.3 | c.3358G>A | p.Asp1120Asn | missense_variant | 22/23 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249450Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135324
GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461380Hom.: 0 Cov.: 29 AF XY: 0.0000261 AC XY: 19AN XY: 727046
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152160Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74344
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 31, 2023 | The c.3580G>A (p.D1194N) alteration is located in exon 24 (coding exon 24) of the SMC1B gene. This alteration results from a G to A substitution at nucleotide position 3580, causing the aspartic acid (D) at amino acid position 1194 to be replaced by an asparagine (N). 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