rs77517267
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_001378454.1(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).
Frequency
Consequence
NM_001378454.1 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.2535C>G | p.Asp845Glu | 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 | ENSP00000482968.1 |
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