rs782781148
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_006306.4(SMC1A):c.298+12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,208,521 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000036 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.000024 ( 0 hom. 6 hem. )
Consequence
SMC1A
NM_006306.4 intron
NM_006306.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.08
Genes affected
SMC1A (HGNC:11111): (structural maintenance of chromosomes 1A) Proper cohesion of sister chromatids is a prerequisite for the correct segregation of chromosomes during cell division. The cohesin multiprotein complex is required for sister chromatid cohesion. This complex is composed partly of two structural maintenance of chromosomes (SMC) proteins, SMC3 and either SMC1B or the protein encoded by this gene. Most of the cohesin complexes dissociate from the chromosomes before mitosis, although those complexes at the kinetochore remain. Therefore, the encoded protein is thought to be an important part of functional kinetochores. In addition, this protein interacts with BRCA1 and is phosphorylated by ATM, indicating a potential role for this protein in DNA repair. This gene, which belongs to the SMC gene family, is located in an area of the X-chromosome that escapes X inactivation. Mutations in this gene result in Cornelia de Lange syndrome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant X-53414969-A-G is Benign according to our data. Variant chrX-53414969-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 259963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Hemizygotes in GnomAdExome4 at 6 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMC1A | NM_006306.4 | c.298+12T>C | intron_variant | ENST00000322213.9 | |||
SMC1A | NM_001281463.1 | c.232+12T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMC1A | ENST00000322213.9 | c.298+12T>C | intron_variant | 1 | NM_006306.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000359 AC: 4AN: 111409Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33573
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GnomAD3 exomes AF: 0.0000111 AC: 2AN: 180932Hom.: 0 AF XY: 0.0000153 AC XY: 1AN XY: 65544
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GnomAD4 exome AF: 0.0000237 AC: 26AN: 1097112Hom.: 0 Cov.: 31 AF XY: 0.0000166 AC XY: 6AN XY: 362506
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GnomAD4 genome ? AF: 0.0000359 AC: 4AN: 111409Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 33573
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Congenital muscular hypertrophy-cerebral syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 01, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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