chr7-103483818-A-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBS1_Supporting
The NM_005045.4(RELN):āc.10016T>Cā(p.Met3339Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000359 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M3339L) has been classified as Likely benign.
Frequency
Consequence
NM_005045.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RELN | NM_005045.4 | c.10016T>C | p.Met3339Thr | missense_variant | 62/65 | ENST00000428762.6 | |
SLC26A5-AS1 | NR_110141.1 | n.1366-20586A>G | intron_variant, non_coding_transcript_variant | ||||
RELN | NM_173054.3 | c.10016T>C | p.Met3339Thr | missense_variant | 62/64 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RELN | ENST00000428762.6 | c.10016T>C | p.Met3339Thr | missense_variant | 62/65 | 5 | NM_005045.4 | P5 | |
SLC26A5-AS1 | ENST00000422488.1 | n.1366-20586A>G | intron_variant, non_coding_transcript_variant | 1 |
Frequencies
GnomAD3 genomes AF: 0.000164 AC: 25AN: 152262Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250708Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135446
GnomAD4 exome AF: 0.0000226 AC: 33AN: 1461674Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 727148
GnomAD4 genome AF: 0.000164 AC: 25AN: 152262Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74390
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Feb 28, 2014 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 30, 2019 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 06, 2018 | - - |
Norman-Roberts syndrome;C4225327:Familial temporal lobe epilepsy 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 12, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at