6-100390178-T-A
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_005068.3(SIM1):c.*183A>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 0.000531 in 634,852 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00057 ( 3 hom. )
Consequence
SIM1
NM_005068.3 3_prime_UTR
NM_005068.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.195
Genes affected
SIM1 (HGNC:10882): (SIM bHLH transcription factor 1) SIM1 and SIM2 genes are Drosophila single-minded (sim) gene homologs. SIM1 transcript was detected only in fetal kidney out of various adult and fetal tissues tested. Since the sim gene plays an important role in Drosophila development and has peak levels of expression during the period of neurogenesis,it was proposed that the human SIM gene is a candidate for involvement in certain dysmorphic features (particularly the facial and skull characteristics), abnormalities of brain development, and/or cognitive disability of Down syndrome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 6-100390178-T-A is Benign according to our data. Variant chr6-100390178-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 354671.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 64 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIM1 | NM_005068.3 | c.*183A>T | 3_prime_UTR_variant | 12/12 | ENST00000369208.8 | ||
SIM1 | NM_001374769.1 | c.*183A>T | 3_prime_UTR_variant | 12/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIM1 | ENST00000369208.8 | c.*183A>T | 3_prime_UTR_variant | 12/12 | 1 | NM_005068.3 | P1 | ||
SIM1 | ENST00000262901.4 | c.*183A>T | 3_prime_UTR_variant | 11/11 | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000427 AC: 65AN: 152232Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.000566 AC: 273AN: 482502Hom.: 3 Cov.: 6 AF XY: 0.000515 AC XY: 129AN XY: 250302
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GnomAD4 genome AF: 0.000420 AC: 64AN: 152350Hom.: 0 Cov.: 32 AF XY: 0.000416 AC XY: 31AN XY: 74508
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Obesity due to SIM1 deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at