rs111980420
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_003126.4(SPTA1):āc.6559A>Gā(p.Lys2187Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,613,230 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_003126.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SPTA1 | NM_003126.4 | c.6559A>G | p.Lys2187Glu | missense_variant | 47/52 | ENST00000643759.2 | NP_003117.2 | |
SPTA1 | XM_011509916.3 | c.6559A>G | p.Lys2187Glu | missense_variant | 48/53 | XP_011508218.1 | ||
SPTA1 | XM_011509917.4 | c.6541A>G | p.Lys2181Glu | missense_variant | 46/51 | XP_011508219.1 | ||
SPTA1 | XM_047428883.1 | c.6238A>G | p.Lys2080Glu | missense_variant | 47/52 | XP_047284839.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SPTA1 | ENST00000643759.2 | c.6559A>G | p.Lys2187Glu | missense_variant | 47/52 | NM_003126.4 | ENSP00000495214.1 | |||
SPTA1 | ENST00000492934.1 | n.74A>G | non_coding_transcript_exon_variant | 2/3 | 2 | |||||
SPTA1 | ENST00000498708.1 | n.-10A>G | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00859 AC: 1308AN: 152192Hom.: 17 Cov.: 32
GnomAD3 exomes AF: 0.00207 AC: 516AN: 249180Hom.: 11 AF XY: 0.00149 AC XY: 202AN XY: 135200
GnomAD4 exome AF: 0.000908 AC: 1327AN: 1460920Hom.: 20 Cov.: 30 AF XY: 0.000772 AC XY: 561AN XY: 726830
GnomAD4 genome AF: 0.00861 AC: 1312AN: 152310Hom.: 17 Cov.: 32 AF XY: 0.00789 AC XY: 588AN XY: 74490
ClinVar
Submissions by phenotype
not provided Benign:4
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Oct 27, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Aug 25, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 16, 2024 | - - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Elliptocytosis 2 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. - |
Hereditary spherocytosis type 3 Benign:1
Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Pyropoikilocytosis, hereditary Benign:1
Likely 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 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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at