chr12-64062921-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_020762.4(SRGAP1):c.806G>A(p.Cys269Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000809 in 1,607,488 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C269V) has been classified as Uncertain significance.
Frequency
Consequence
NM_020762.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SRGAP1 | NM_020762.4 | c.806G>A | p.Cys269Tyr | missense_variant | 7/22 | ENST00000355086.8 | |
SRGAP1 | NM_001346201.2 | c.806G>A | p.Cys269Tyr | missense_variant | 7/22 | ||
SRGAP1 | XM_024449096.2 | c.806G>A | p.Cys269Tyr | missense_variant | 7/14 | ||
SRGAP1 | XM_024449097.2 | c.806G>A | p.Cys269Tyr | missense_variant | 7/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SRGAP1 | ENST00000355086.8 | c.806G>A | p.Cys269Tyr | missense_variant | 7/22 | 1 | NM_020762.4 | A1 | |
ENST00000535594.1 | n.134-19981C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000825 AC: 12AN: 1455372Hom.: 0 Cov.: 31 AF XY: 0.00000415 AC XY: 3AN XY: 723290
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152116Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74314
ClinVar
Submissions by phenotype
Congenital anomaly of kidney and urinary tract Pathogenic:2
Pathogenic, no assertion criteria provided | literature only | Yale Center for Mendelian Genomics, Yale University | May 31, 2015 | - - |
Pathogenic, no assertion criteria provided | literature only | Yale Center for Mendelian Genomics, Yale University | Aug 24, 2018 | - - |
Nephronophthisis Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard | May 28, 2020 | The heterozygous p.Cys269Tyr variant in SRGAP1 was identified by our study in 1 individual with nephronophthisis, as well as this individual's mother whose affection status is unknown (PMID: 26026792). This variant was absent from large population studies. In vitro functional studies provide some evidence that the p.Cys269Tyr variant may slightly impact protein function (PMID: 26026792). However, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. Furthermore, although this gene has been reported in association with nephronophthisis, it currently has limited evidence for these associations. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PS3_supporting (Richards 2015). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at