rs112727682
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_006306.4(SMC1A):c.*14C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00565 in 1,168,433 control chromosomes in the GnomAD database, including 10 homozygotes. There are 1,986 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0043 ( 1 hom., 133 hem., cov: 22)
Exomes 𝑓: 0.0058 ( 9 hom. 1853 hem. )
Consequence
SMC1A
NM_006306.4 3_prime_UTR
NM_006306.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.679
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant X-53380089-G-A is Benign according to our data. Variant chrX-53380089-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 159937.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00434 (482/111102) while in subpopulation NFE AF= 0.00742 (393/52982). AF 95% confidence interval is 0.00681. There are 1 homozygotes in gnomad4. There are 133 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
High Hemizygotes in GnomAd4 at 133 XL gene
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SMC1A | ENST00000322213 | c.*14C>T | 3_prime_UTR_variant | Exon 25 of 25 | 1 | NM_006306.4 | ENSP00000323421.3 | |||
| SMC1A | ENST00000375340 | c.*14C>T | 3_prime_UTR_variant | Exon 26 of 26 | 1 | ENSP00000364489.7 | ||||
| SMC1A | ENST00000675504 | c.*14C>T | 3_prime_UTR_variant | Exon 25 of 25 | ENSP00000502524.1 | |||||
| SMC1A | ENST00000674590 | c.*14C>T | 3_prime_UTR_variant | Exon 23 of 23 | ENSP00000502626.1 |
Frequencies
GnomAD3 genomes 0.00435 AC: 483AN: 111049Hom.: 1 Cov.: 22 AF XY: 0.00400 AC XY: 133AN XY: 33259
GnomAD3 genomes
AF:
AC:
483
AN:
111049
Hom.:
Cov.:
22
AF XY:
AC XY:
133
AN XY:
33259
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00429 AC: 767AN: 178732Hom.: 5 AF XY: 0.00436 AC XY: 281AN XY: 64380
GnomAD3 exomes
AF:
AC:
767
AN:
178732
Hom.:
AF XY:
AC XY:
281
AN XY:
64380
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00578 AC: 6116AN: 1057331Hom.: 9 Cov.: 26 AF XY: 0.00560 AC XY: 1853AN XY: 330919
GnomAD4 exome
AF:
AC:
6116
AN:
1057331
Hom.:
Cov.:
26
AF XY:
AC XY:
1853
AN XY:
330919
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome 0.00434 AC: 482AN: 111102Hom.: 1 Cov.: 22 AF XY: 0.00399 AC XY: 133AN XY: 33322
GnomAD4 genome
AF:
AC:
482
AN:
111102
Hom.:
Cov.:
22
AF XY:
AC XY:
133
AN XY:
33322
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
History of neurodevelopmental disorder Uncertain:1
Jan 10, 2013
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
There is insufficient or conflicting evidence for classification of this alteration. -
not specified Benign:1
Feb 08, 2013
Genetic Services Laboratory, University of Chicago
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
De Lange syndrome Benign:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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