11-121452543-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_003105.6(SORL1):c.212G>A(p.Arg71His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000447 in 1,343,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_003105.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SORL1 | NM_003105.6 | c.212G>A | p.Arg71His | missense_variant | Exon 1 of 48 | ENST00000260197.12 | NP_003096.2 | |
SORL1-AS1 | NR_183636.1 | n.293+132C>T | intron_variant | Intron 1 of 2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SORL1 | ENST00000260197.12 | c.212G>A | p.Arg71His | missense_variant | Exon 1 of 48 | 1 | NM_003105.6 | ENSP00000260197.6 | ||
SORL1 | ENST00000532451.1 | n.164G>A | non_coding_transcript_exon_variant | Exon 1 of 15 | 1 | |||||
SORL1-AS1 | ENST00000501964.1 | n.339+132C>T | intron_variant | Intron 1 of 1 | 2 | |||||
SORL1-AS1 | ENST00000529160.1 | n.245+132C>T | intron_variant | Intron 1 of 1 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000447 AC: 6AN: 1343040Hom.: 0 Cov.: 31 AF XY: 0.00000755 AC XY: 5AN XY: 662268
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.212G>A (p.R71H) alteration is located in exon 1 (coding exon 1) of the SORL1 gene. This alteration results from a G to A substitution at nucleotide position 212, causing the arginine (R) at amino acid position 71 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 71 of the SORL1 protein (p.Arg71His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with SORL1-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at