rs77517267
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The ENST00000613296.6(ALMS1):āc.2535C>Gā(p.Asp845Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. D845D) has been classified as Benign.
Frequency
Consequence
ENST00000613296.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALMS1 | NM_001378454.1 | c.2535C>G | p.Asp845Glu | missense_variant | 8/23 | ENST00000613296.6 | NP_001365383.1 | |
ALMS1 | NM_015120.4 | c.2538C>G | p.Asp846Glu | missense_variant | 8/23 | NP_055935.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALMS1 | ENST00000613296.6 | c.2535C>G | p.Asp845Glu | missense_variant | 8/23 | 1 | NM_001378454.1 | ENSP00000482968 | P3 |
Frequencies
GnomAD3 genomes AF: 0.000611 AC: 93AN: 152170Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000169 AC: 42AN: 248886Hom.: 0 AF XY: 0.000141 AC XY: 19AN XY: 134998
GnomAD4 exome AF: 0.0000780 AC: 114AN: 1461796Hom.: 0 Cov.: 40 AF XY: 0.0000688 AC XY: 50AN XY: 727206
GnomAD4 genome AF: 0.000644 AC: 98AN: 152288Hom.: 0 Cov.: 33 AF XY: 0.000631 AC XY: 47AN XY: 74480
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | ALMS1: BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 23, 2024 | Reported as a heterozygous variant in a pediatric patient with HCM who also harbored variants in autosomal dominant genes (PMID: 32746448); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32746448, 26582918) - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 24, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Alstrom syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at