4-25121808-T-C
Position:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_016955.4(SEPSECS):c.*2123A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00578 in 152,300 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0058 ( 9 hom., cov: 33)
Consequence
SEPSECS
NM_016955.4 3_prime_UTR
NM_016955.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 4.88
Genes affected
SEPSECS (HGNC:30605): (Sep (O-phosphoserine) tRNA:Sec (selenocysteine) tRNA synthase) The amino acid selenocysteine is the only amino acid that does not have its own tRNA synthetase. Instead, this amino acid is synthesized on its cognate tRNA in a three step process. The protein encoded by this gene catalyzes the third step in the process, the conversion of O-phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec).[provided by RefSeq, Mar 2011]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.25).
BP6
Variant 4-25121808-T-C is Benign according to our data. Variant chr4-25121808-T-C is described in ClinVar as [Benign]. Clinvar id is 348528.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00578 (880/152300) while in subpopulation AFR AF= 0.0199 (829/41570). AF 95% confidence interval is 0.0188. There are 9 homozygotes in gnomad4. There are 427 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 9 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SEPSECS | NM_016955.4 | c.*2123A>G | 3_prime_UTR_variant | 11/11 | ENST00000382103.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEPSECS | ENST00000382103.7 | c.*2123A>G | 3_prime_UTR_variant | 11/11 | 1 | NM_016955.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00576 AC: 877AN: 152182Hom.: 9 Cov.: 33
GnomAD3 genomes
AF:
AC:
877
AN:
152182
Hom.:
Cov.:
33
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:
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
GnomAD4 genome AF: 0.00578 AC: 880AN: 152300Hom.: 9 Cov.: 33 AF XY: 0.00573 AC XY: 427AN XY: 74482
GnomAD4 genome
AF:
AC:
880
AN:
152300
Hom.:
Cov.:
33
AF XY:
AC XY:
427
AN XY:
74482
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:
Asia WGS
AF:
AC:
5
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Pontocerebellar hypoplasia type 2D Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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