chr6-52492306-A-G
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_018100.4(EFHC1):āc.1888A>Gā(p.Asn630Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,916 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 Uncertain significance (ā ).
Frequency
Consequence
NM_018100.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EFHC1 | NM_018100.4 | c.1888A>G | p.Asn630Asp | missense_variant | 11/11 | ENST00000371068.11 | |
EFHC1 | NM_001172420.2 | c.1831A>G | p.Asn611Asp | missense_variant | 12/12 | ||
EFHC1 | NR_033327.2 | n.3214A>G | non_coding_transcript_exon_variant | 10/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EFHC1 | ENST00000371068.11 | c.1888A>G | p.Asn630Asp | missense_variant | 11/11 | 1 | NM_018100.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152208Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251228Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135798
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461708Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727162
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152208Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74348
ClinVar
Submissions by phenotype
Absence seizure;C1850778:Myoclonic epilepsy, juvenile, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 03, 2020 | This variant is present in population databases (rs747171841, ExAC 0.03%). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with EFHC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 465666). This sequence change replaces asparagine with aspartic acid at codon 630 of the EFHC1 protein (p.Asn630Asp). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and aspartic acid. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at